Reglan

Boxed Warning 02/2026 Indications and Usage ( 1 ) 02/2026 Dosage and Administration ( 2.1 , 2.2 ) 02/2026 Warnings and Precautions, Tardive Dyskinesia ( 5.1 ) 02/2026 Warnings and Precautions, Other Extrapyramidal Symptoms ( 5.2 ) 02/2026

1 INDICATIONS AND USAGE Reglan tablets are indicated for the: • 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. Limitations of Use : • Reglan has not been shown to be safe and effective for the treatment of symptomatic, documented gastroesophageal reflux for longer than 12 weeks [see Warnings and Precautions ( 5.1 )] . • Reglan 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 )]. Reglan tablets are indicated for the: • Treatment for 4 to 12 weeks of symptomatic, documented gastroesophageal reflux in adults who fail to respond to conventional therapy ( 1 ) • Relief of symptoms in adults with acute and recurrent diabetic gastroparesis ( 1 ) Limitations of Use: • Reglan has not been shown to be safe and effective for the gastroesophageal reflux for longer than 12 weeks ( 1 , 5.1 ). • Reglan tablets are 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 ( 1 , 8.4 )

2 DOSAGE AND ADMINISTRATION Symptomatic, Documented Gastroesophageal Reflux in Adults Who Fail Conventional Therapy ( 2.1 ) • Administer Reglan continuously or intermittently: ○ Continuous: The recommended dosage is 10 to 15 mg orally, 30 minutes before each meal and at bedtime (maximum of 60 mg per day) for 4 to 12 weeks, as determined by endoscopic response. ○ Intermittent: Single doses up to 20 mg prior to provoking situation. Acute and Recurrent Diabetic Gastroparesis in Adults ( 2.2 ) • The recommended dosage is 10 mg orally, 30 minutes before each meal and at bedtime (maximum of 40 mg per day). Dosage Adjustment in Specific Populations ( 2.1 , 2.2 ) • For symptomatic, documented gastroesophageal reflux and acute and recurrent diabetic gastroparesis, see Full Prescribing Information for recommended dosage reductions for elderly patients, in patients with moderate or severe hepatic or renal impairment, and cytochrome P450 2D6 (CYP2D6) poor metabolizers. 2.1 Recommended Dosage for Symptomatic, Documented Gastroesophageal Reflux in Adults Who Fail Conventional Therapy Reglan tablets may be administered continuously or intermittently in patients with symptomatic, documented gastroesophageal reflux who fail to respond to conventional therapy: Continuous Dosing • The recommended dosage of Reglan tablets is 10 to 15 mg orally four times daily. The maximum recommended daily oral dosage is 60 mg. • Administer each dose thirty minutes before a meal and at bedtime. • The recommended treatment duration is 4 to 12 weeks, as determined by endoscopic response. Use Reglan for the shortest duration of treatment and periodically reassess the need for continued treatment. • The maximum recommended duration of treatment is 12 weeks [see Warnings and Precautions ( 5.1 )] . 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 Reglan as a single dose up to 20 mg prior to the provoking situation. Consider dosage reductions for the populations and situations in Table 1. Table 1. Recommended Dosage of Reglan Tablets for Symptomatic, Documented Gastroesophageal Reflux in Adults Who Fail Conventional Therapy Recommended Dosage Maximum Recommended Daily Dosage Adult patients 10 to 15 mg four times daily (thirty minutes before each meal and at bedtime) 60 mg Mild hepatic impairment (Child-Pugh A) Elderly patients [see Use in Specific Populations ( 8.5 )] 5 mg 1 four times daily (thirty minutes before each meal and at bedtime) Moderate or severe hepatic impairment (Child-Pugh B or C) [see Use in Specific Populations ( 8.7 )] 5 mg four times daily (thirty minutes before each meal and at bedtime), or 10 mg taken three times daily 30 mg CYP2D6 poor metabolizers [see Use in Specific Populations ( 8.9 )] Concomitant use with strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine) [see Drug Interactions ( 7.1 )] Moderate or severe renal impairment (creatinine clearance less than or equal to 60 mL/minute) [see Use in Specific Populations ( 8.6 )] Patients with End-Stage Renal Disease (ESRD ) including those treated with hemodialysis and continuous ambulatory peritoneal dialysis [see Use in Specific Populations ( 8.6 )] 5 mg four times daily (thirty minutes before each meal and at bedtime) or 10 mg twice daily 20 mg 1 Elderly patients may be more sensitive to the therapeutic or adverse effects of Reglan; 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. 2.2 Recommended Dosage for Acute and Recurrent Diabetic …

3 DOSAGE FORMS AND STRENGTHS Tablets: • 5 mg metoclopramide: green, elliptical-shaped, debossed “REGLAN” over “5” on one side and “ANI” on the opposite side • 10 mg metoclopramide: white, double edge scored, capsule-shaped, debossed “REGLAN” on one side and “ANI 10” on the opposite side Tablets: 5 mg and 10 mg metoclopramide ( 3 )

4 CONTRAINDICATIONS Reglan is contraindicated: • 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. Reglan may cause a hypertensive/pheochromocytoma crisis, probably due to release of catecholamines from the tumor [see Warnings and Precautions ( 5.5 )] . • In patients with epilepsy. Reglan may increase the frequency and severity of seizures [see Adverse Reactions ( 6 )] . • In patients with hypersensitivity to metoclopramide. Reactions have included laryngeal and glossal angioedema and bronchospasm [see Adverse Reactions ( 6 )] . • History of TD or dystonic reaction to metoclopramide ( 4 ) • When stimulation of gastrointestinal motility might be dangerous ( 4 ) • Pheochromocytoma, catecholamine-releasing paragangliomas ( 4 ) • Epilepsy ( 4 ) • Hypersensitivity to metoclopramide ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are described, or described in greater detail, in other sections of the labeling: • Tardive dyskinesia [see Boxed Warning and Warnings and Precautions ( 5.1 )] • Other extrapyramidal symptoms [see Warnings and Precautions ( 5.2 )] • Neuroleptic malignant syndrome [see Warnings and Precautions ( 5.3 )] • Depression [see Warnings and Precautions ( 5.4 )] • Hypertension [see Warnings and Precautions ( 5.5 )] • Fluid retention [see Warnings and Precautions ( 5.6 )] • Hyperprolactinemia [see Warnings and Precautions ( 5.7 )] • Effects on the ability to drive and operate machinery [see Warnings and Precautions ( 5.8 )] 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. Adverse reactions, especially those involving the nervous system, occurred after stopping metoclopramide including dizziness, nervousness, and headaches. Central Nervous System Disorders • 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). 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 • Most common adverse reactions (> 10%) are restlessness, drowsiness, fatigue, and lassitude. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc. at 1-855-204-1431 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 DRUG INTERACTIONS • Antipsychotics : Potential for additive effects, including TD, EPS, and NMS; avoid concomitant use. ( 7.1 ) • Central Nervous System (CNS) depressants : Increased risk of CNS depression. Avoid concomitant use and monitor for adverse reactions. ( 7.1 ) • Strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine) : See Full Prescribing Information for recommended dosage reductions. ( 2.1 , 2.2 , 7.1 ) • Monoamine oxidase (MAO) inhibitors : Increased risk of hypertension; avoid concomitant use. ( 5.5 , 7.1 ) • Additional drug interactions : See Full Prescribing Information. ( 7.1 , 7.2 ) 7.1 Effects of Other Drugs on Metoclopramide Table 3 displays the effects of other drugs on metoclopramide. Table 3. Effects of Other Drugs on Metoclopramide Antipsychotics Clinical Impact Potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Intervention Avoid concomitant use [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 )] . Strong CYP2D6 Inhibitors, not Included in Antipsychotic Category Above Clinical Impact Increased plasma concentrations of metoclopramide; risk of exacerbation of extrapyramidal symptoms [see Clinical Pharmacology ( 12.3 )] . Intervention Reduce the Reglan dosage [see Dosage and Administration ( 2.1 , 2.2 )] . Examples quinidine, bupropion, fluoxetine, and paroxetine Monoamine Oxidase Inhibitors Clinical Impact Increased risk of hypertension [see Warnings and Precautions ( 5.5 )] . Intervention Avoid concomitant use. Central Nervous System (CNS) Depressants Clinical Impact Increased risk of CNS depression [see Warnings and Precautions ( 5.8 )] . Intervention Avoid Reglan or the interacting drug, depending on the importance of the drug to the patient. Examples alcohol, sedatives, hypnotics, opiates and anxiolytics Drugs that Impair Gastrointestinal Motility Clinical Impact Decreased systemic absorption of metoclopramide. Intervention Monitor for reduced therapeutic effect. Examples antiperistaltic antidiarrheal drugs, anticholinergic drugs, and opiates Dopaminergic Agonists and Other Drugs that Increase Dopamine Concentrations Clinical Impact Decreased therapeutic effect of metoclopramide due to opposing effects on dopamine. Intervention Monitor for reduced therapeutic effect. Examples apomorphine, bromocriptine, cabergoline, levodopa, pramipexole, ropinirole, and rotigotine 7.2 Effects of Metoclopramide on Other Drugs Table 4 displays the effects of metoclopramide on other drugs. Table 4. Effects of Metoclopramide on Other Drugs Dopaminergic Agonists and Drugs Increasing Dopamine Concentrations Clinical Impact Opposing effects of metoclopramide and the interacting drug on dopamine. Potential exacerbation of symptoms (e.g., parkinsonian symptoms). Intervention Avoid concomitant use [see Warnings and Precautions ( 5.2 )] . Examples Apomorphine, bromocriptine, cabergoline, levodopa, pramipexole, ropinirole, rotigotine Succinylcholine, Mivacurium Clinical Impact Metoclopramide inhibits plasma cholinesterase leading to enhanced neuromuscular blockade. Intervention Monitor for signs and symptoms of prolonged neuromuscular blockade. Drugs with Absorption Altered due to Increased Gastrointestinal Motility Clinical Impact The effect of metoclopramide on other drugs is variable. Increased gastrointestinal (GI) motility by metoclopramide may impact absorption of other drugs leading to decreased or increased drug exposure. Intervention Drugs with Decreased Absorption (e.g., digoxin, atovaquone, posaconazole oral suspension*, fosfomycin) : Monitor for reduced therapeutic effect of the interacting drug. For digoxin monitor therapeutic drug concentrations and increase the digoxin dose as needed (see prescribing information for digoxin). Drugs with Increased Absorption (e.g., sirolimus, tacrolimus, cyclosporine) : Monitor therapeutic drug concentrations and adjust the …

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 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 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. 8.2 Lactation Risk Summary Limited published data report the presence of metoclopramide in human milk in variable amounts (see Data) . 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 Reglan and any potential adverse effects on the breastfed child from Reglan 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. 8.4 Pediatric Use 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 Reglan tablets 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 b 5 reductase, making them more susceptible to methemoglobinemia, a possible adverse reaction of metoclopramide use in neonates [see Use in Specific Populations ( 8.8 )] . 8.5 Geriatric Use 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 wit …

12.1 Mechanism of Action 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.

11 DESCRIPTION Metoclopramide hydrochloride, the active ingredient of Reglan, 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-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxy benzamide monohydrochloride monohydrate. The molecular formula is C 14 H 22 ClN 3 O 2 •HCl•H 2 O. Its molecular weight is 354.3. The structural formula is: Reglan tablets are for oral administration. Reglan is available in 5 mg and 10 mg tablets. • Each Reglan 5 mg tablet contains 5 mg metoclopramide (equivalent to 5.91 mg of metoclopramide hydrochloride USP). Inactive ingredients consist of corn starch, D&C Yellow 10 Aluminum Lake, FD&C Blue 1 Aluminum Lake, lactose, microcrystalline cellulose, silicon dioxide, and stearic acid. • Each Reglan 10 mg tablet contains 10 mg metoclopramide (equivalent to 11.82 mg metoclopramide hydrochloride USP). Inactive ingredients consist of magnesium stearate, mannitol, microcrystalline cellulose, and stearic acid. structure

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

16 HOW SUPPLIED/STORAGE AND HANDLING Each green, elliptical-shaped Reglan tablet contains 5 mg metoclopramide. The tablet is debossed “REGLAN” over “5” on one side and “ANI” on the opposite side. Available in bottles of 100 tablets (NDC 62559-165-01) Each white, double edge scored, capsule-shaped Reglan tablet contains 10 mg metoclopramide. The tablet is debossed “REGLAN” on one side and “ANI 10” on the opposite side. Available in bottles of 100 tablets (NDC 62559-166-01) Dispense tablets in tight, light-resistant container. Store tablets at controlled room temperature between 20°C and 25°C (68°F and 77°F).