Metoclopramide: uses, appearance and warnings

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. ( 1 ) Relief of symptoms in adults with acute and recurrent diabetic gastroparesis. ( 1 ) Limitations of Use: Metoclopramide tablets have not been shown to be safe and effective for the treatment of gastroesophageal reflux for longer than 12 weeks. ( 1 , 5.1 ) Metoclopramide 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 ) 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. Relief of symptoms in adults with acute and recurrent diabetic gastroparesis. Limitations of Use : Metoclopramide 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 )]. 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 )].

Tablets: 5 mg and 10 mg metoclopramide ( 3 ) Tablets: Metoclopramide tablets, USP 5 mg are white to off white, oval shaped, biconvex tablets with "RF10" debossed on one side and plain on the other side. Metoclopramide tablets, USP 10 mg are white to off white, capsule shaped, biconvex tablets, with "RF11" debossed on one side and score line on the other side

Each white to off white, capsule shaped, biconvex metoclopramide tablet, USP contains 10 mg of metoclopramide base as metoclopramide hydrochloride, USP. The tablets have "RF11" debossed on one side and score line on the other side. Available in: Bottle of 30 tablets NDC 83980-011-13 Bottle of 100 tablets NDC 83980-011-01 Bottle of 500 tablets NDC 83980-011-05 Bottle of 1,000 tablets NDC 83980-011-10 Each white to off white, oval shaped, biconvex metoclopramide tablet, USP contains 5 mg of metoclopramide base as metoclopramide hydrochloride, USP. The tablets have "RF10" debossed on one side and plain on the other side. Available in: Bottle of 30 tablets NDC 83980-010-13 Bottle of 100 tablets NDC 83980-010-01 Bottle of 500 tablets NDC 83980-010-05 Bottle of 1,000 tablets NDC 83980-010-10 Dispense tablets in tight, light-resistant container. Store between 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature].

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 ) Metoclopramide 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. Metoclopramide 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 Metoclopramide 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 )] .

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. ( 5.1 , 5.2 , 5.3 , 7.1 , 7.2 ) Depression and suicidal ideation/suicide : Avoid use. ( 5.4 ) 5.1 Tardive Dyskinesia Metoclopramide, including metoclopramide tablets, 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 metoclopramide tablets, 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 this symptomatic suppression upon the long-term course of TD is unknown. TD may remit, partially or completely, if metoclopramide tablets treatment is discontinued. In patients treated with metoclopramide, including metoclopramide tablets, 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 [see Use in Specific Populations ( 8.5 )] , and in patients with diabetes mellitus. Prevention, Mitigation, and Monitoring for TD Metoclopramide tablet is contraindicated in patients with a history of TD. Avoid use of metoclopramide tablet in patients receiving concomitant antipsychotics due to the potential additive effects of TD [see Drug Interactions ( 7.1 )]. Reduce the metoclopramide tablet dosage in the elderly [see Dosage and Administration ( 2.1 , 2.2 )]. Use metoclopramide tablets for the shortest duration of treatment and periodically reassess the need for continued treatment. Immediately discontinue metoclopramide tablet in patients who develop signs and symptoms of TD. In patients with symptomatic, documented gastroesophageal reflux, the maximum duration of treatment is 12 weeks [see Dosage and Administration ( 2.2 )]. In patients with diabetic gastroparesis, avoid a total duration of treatment with metoclopramide products, including metoclopramide tablets, 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. 5.2 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 metoclopramide. 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 higher than recommended dosages. EPS occurred more frequently in pediatric patients compared to adults (metoclopramide is not approved for use in pediatric patients). 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 metoclopramide 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 metoclopramide 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 metoclopramide tablet for shortest duration of treatment and periodically reassess the need for continued treatment. Routinely monitor for signs and symptoms of Parkinson's disease [see Dosage and Administration ( 2.1 , 2.2 )] . 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. 5.3 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 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 anticholinergictoxicity, heat stroke, malignant hyperthermia, drug fever, serotonin syndrome, and primary central nervous system pathology. …

Most common adverse reactions (> 10%) are restlessness, drowsiness, fatigue, and lassitude. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Ipca at 1-888-472-2651 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 ide …

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 ,2.3, 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. …