Reference ID: 4145755 - accessdata.fda.gov

1 HIGHLIGHTS OF PRESCRIBING INFORMATION Acute and Recurrent Diabetic Gastroparesis ( ). These highlights do not include all the information needed to use REGLAN Administer 10 mg, 30 minutes before each meal and at bedtime (maximum TABLETS safely and effectively. See full prescribing information for of 40 mg per day) for 2 to 8 weeks REGLAN TABLETS. Dosage Adjustment in Specific Populations ( , ). For gastroesophageal reflux and acute and recurrent diabetic gastroparesis, REGLAN (metoclopramide) tablets, for oral use see Full Prescribing Information for recommended dosage reductions for Initial Approval: 1979 elderly patients, in patients with moderate or severe hepatic or renal impairment, and cytochrome p450 2D6 (CYP2D6) poor metabolizers. WARNING: TARDIVE DYSKINESIA. See full prescribing information for complete boxed warning. ---------------------DOSAGE FORMS AND STRENGTHS.

2 Tablets: 5 mg and 10 mg metoclopramide (3). Reglan can cause tardive dyskinesia (TD), a serious movement disorder that is often irreversible. There is no known treatment for TD. The risk ------------------------------CONTRAINDI CATIONS------------------------------ . of developing TD increases with duration of treatment and total History of TD or dystonic reaction to metoclopramide (4). cumulative dosage ( ) When stimulation of gastrointestinal motility might be dangerous (4). Discontinue Reglan in patients who develop signs or symptoms of TD Pheochromocytoma, catecholamine-releasing paragangliomas (4). ( ) Epilepsy (4). Avoid treatment with Reglan for longer than 12 weeks because of the Hypersensitivity to metoclopramide (4). risk of developing TD with longer-term use ( , , , ). -----------------------WARNINGS AND PRECAUTIONS----------------------- . ----------------------------RECENT MAJOR CHANGES------------------------- Tardive Dyskinesia (TD), Other Extrapyramidal Symptoms (EPS), and Boxed Warning 8/2017 Neuroleptic Malignant Syndrome (NMS): Avoid concomitant use of other Indications and Usage (1) 8/2017 drugs known to cause TD/EPS/NMS and avoid use in patients with Dosage and Administration, Dosage for Gastroesophageal Reflux ( ) 8/2017 Parkinson's Disease.

3 If symptoms occur, discontinue Reglan and seek Dosage and Administration, Dosage for Acute and Recurrent Diabetic immediate medical attention. ( , , , , ). Gastroparesis ( ) 8/2017 Depression and suicidal ideation/suicide: Avoid use. ( ). Contraindications (4) 8/2017. Warnings and Precautions, Tardive Dyskinesia ( ) 8/2017 ------------------------------ADVERSE REACTIONS------------------------------ . Warnings and Precautions, Other Extrapyramidal Symptoms ( ) 8/2017 Most common adverse reactions (> 10%) are restlessness, drowsiness, Warnings and Precautions, Neuroleptic Malignant Syndrome ( ) 8/2017 fatigue, and lassitude. (6). Warnings and Precautions, Hyperprolactinemia ( ) 8/2017. To report SUSPECTED ADVERSE REACTIONS, contact ANI. ----------------------------INDICATIONS AND USAGE--------------------------- Pharmaceuticals, Inc. at 1-800-308-6755 or FDA at 1-800-FDA-1088 or 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.

4 (1) ------------------------------DRUG INTERACTIONS---------------------------- -- . Relief of symptoms in adults with acute and recurrent diabetic gastroparesis. Antipsychotics: Potential for additive effects, including TD, EPS, and (1) NMS; avoid concomitant use. ( ). CNS depressants: Increased risk of CNS depression. Avoid concomitant Limitations of Use: use and monitor for adverse reactions. ( ). Reglan tablets are not recommended for use in pediatric patients due to the risk Strong CYP2D6 inhibitors ( , quinidine, bupropion, fluoxetine, and of tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the paroxetine): See Full Prescribing Information for recommended dosage risk of methemoglobinemia in neonates. (1, ) reductions. ( , , ). MAO inhibitors: Increased risk of hypertension; avoid concomitant use. ------------------------DOSAGE AND ADMINISTRATION---------------------- ( , ).

5 Gastroesophageal Reflux ( ) Additional drug interactions: See Full Prescribing Information. ( , ). Administer Reglan continuously or intermittently: o Continuous: Administer 10 to 15 mg, 30 minutes before each meal and at See 17 for PATIENT COUNSELING INFORMATION and Medication bedtime (maximum of 60 mg per day) for 4 to 12 weeks. Guide. o Intermittent: Single doses up to 20 mg prior to provoking situation. Revised: 08/2017. _____. FULL PRESCRIBING INFORMATION: CONTENTS* 8 USE IN SPECIFIC POPULATIONS. Pregnancy WARNING: TARDIVE DYSKINESIA Lactation 1 INDICATIONS AND USAGE Pediatric Use 2 DOSAGE AND ADMINISTRATION Geriatric Use Important Administration Instructions Renal Impairment Dosage for Gastroesophageal Reflux Hepatic Impairment Dosage for Acute and Recurrent Diabetic Gastroparesis NADH-Cytochrome b5 Reductase Deficiency 3 DOSAGE FORMS AND STRENGTHS CYP2D6 Poor Metabolizers 4 CONTRAINDICATIONS 10 OVERDOSAGE.

6 5 WARNINGS AND PRECAUTIONS 11 DESCRIPTION. Tardive Dyskinesia 12 CLINICAL PHARMACOLOGY. Other Extrapyramidal Symptoms Mechanism of Action Neuroleptic Malignant Syndrome Pharmacodynamics Depression Pharmacokinetics Hypertension 13 NONCLINICAL TOXICOLOGY. Fluid Retention Carcinogenesis, Mutagenesis, Impairment of Fertility Hyperprolactinemia 16 HOW SUPPLIED/STORAGE AND HANDLING. Effects on the Ability to Drive and Operate Machinery 17 PATIENT COUNSELING INFORMATION. 6 ADVERSE REACTIONS. 7 DRUG INTERACTIONS *Sections or subsections omitted from the full prescribing information are not Effects of Other Drugs on Metoclopramide listed. Effects of Metoclopramide on Other Drugs _____. Reference ID: 4145755 1. FULL PRESCRIBING INFORMATION. WARNING: TARDIVE DYSKINESIA. Reglan can cause tardive dyskinesia (TD), a serious movement disorder that is often irreversible. There is no known treatment for TD.

7 The risk of developing TD. increases with duration of treatment and total cumulative dosage [see Warnings and Precautions ( )]. Discontinue Reglan in patients who develop signs or symptoms of TD. In some patients, symptoms may lessen or resolve after Reglan is stopped [see Warnings and Precautions ( )]. Avoid treatment with Reglan for longer than 12 weeks because of the increased risk of developing TD with longer-term use [see Warnings and Precautions ( ) and Dosage and Administration ( , )]. 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 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 2 DOSAGE AND ADMINISTRATION. Important Administration Instructions Avoid treatment with Reglan for longer than 12 weeks because of the increased risk of developing TD with longer-term use [see Dosage and Administration ( , ), Warnings and Precautions ( )]. Dosage for Gastroesophageal Reflux Reglan 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 Reglan 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. 2. Reference ID: 4145755 . 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.

9 (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 in 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 Reglan Tablet Dosage in Patients with Gastroesophageal Reflux Maximum Recommended Dosage Recommended Daily Dosage Adult patients 10 to 15 mg four times daily (thirty minutes before each Mild hepatic impairment (Child-Pugh A) meal and at bedtime). 60 mg 5 mg1 four times daily (thirty Elderly patients [see Use in Specific Populations ( )] minutes before each meal and at bedtime). Moderate or severe hepatic impairment (Child-Pugh B or C) [see Use in Specific Populations ( )]. CYP2D6 poor metabolizers [see Use in Specific Populations ( )] 5 mg four times daily (thirty Concomitant use with strong CYP2D6 inhibitors ( , minutes before each meal and 30 mg quinidine, bupropion, fluoxetine, and paroxetine) [see at bedtime), or Drug Interactions ( )] 10 mg taken three times daily Moderate or severe renal impairment (creatinine clearance less than or equal to 60 mL/minute) [see Use in Specific Populations ( )].

10 Patients with End-Stage Renal Disease (ESRD) including 5 mg four times daily (thirty those treated with hemodialysis and continuous minutes before each meal and 20 mg ambulatory peritoneal dialysis [see Use in Specific at bedtime) or 10 mg twice Populations ( )] daily 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. Dosage for Acute and Recurrent Diabetic Gastroparesis 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 Reglan treatment for greater than 12 weeks [see Warnings and Precautions ( )]. Administer the dosage thirty minutes before each meal and at bedtime.