Metoclopramide

Metoclopramide Tablets USP 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: • Metoclopramide Tablets USP have not been shown to be safe and effective for the treatment of symptomatic, documented gastroesophageal reflux for longer than 12 weeks. • Metoclopramide Tablets USP 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. Metoclopramide 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.

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.

Symptomatic, Documented Gastroesophageal Reflux in Adults Who Fail Conventional Therapy. • Administer metoclopramide tablets continuously or intermittently: o 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. o Intermittent: Single doses up to 20 mg prior to provoking situation. Acute and Recurrent Diabetic Gastroparesis in Adults. • 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.

Metoclopramide tablets are contraindicated: • In patients with a history of tardive dyskinesia (TD) or a dystonic reaction to metoclopramide. • 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. • In patients with epilepsy. Metoclopramide may increase the frequency and severity of seizures. • In patients with hypersensitivity to metoclopramide.

Boxed warning (tardive dyskinesia •): Metoclopramide, including metoclopramide tablets, can cause tardive dyskinesia (TD), a potentially irreversible serious movement disorder. In patients treated with metoclopramide, including metoclopramide tablets, the risk of developing TD increases with duration of treatment and total cumulative dosage. • Metoclopramide tablets are contraindicated in patients with a history of TD. • Tardive Dyskinesia (TD), Other Extrapyramidal Symptoms (EPS), and Neuroleptic Malignant Syndrome (NMS): Avoid concomitant use of other drugs known to cause TD/EPS/NMS and avoid use in patients with Parkinson’s Disease. If symptoms occur, discontinue metoclopramide tablets and seek immediate medical attention. • Depression and suicidal ideation/suicide: Avoid use.

The following adverse reactions are described, or described in greater detail, in other sections of the labeling: • Tardive dyskinesia • Other extrapyramidal symptoms • Neuroleptic malignant syndrome • Depression • Hypertension • Fluid retention • Hyperprolactinemia • Effects on the ability to drive and operate machinery 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.

• Antipsychotics: Potential for additive effects, including TD, EPS, and NMS, avoid concomitant use. • Central Nervous System (CNS) depressants: Increased risk of CNS depression. Avoid concomitant use and monitor for adverse reactions. • Strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine): See Full Prescribing Information for recommended dosage reductions. • Monoamine oxidase (MAO) inhibitors: Increased risk of hypertension, avoid concomitant use. • Additional drug interactions: See Full Prescribing Information.

Store tablets at controlled room temperature between 20°C and 25°C (68°F and 77°F).