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 dose as needed. See prescribing information for the interacting drug.
Insulin Clinical Impact
Increased GI motility by metoclopramide may increase delivery of food to the intestines and increase blood glucose.
Intervention
Monitor blood glucose and adjust insulin dosage regimen as needed. * Interaction does not apply to posaconazole delayed-release tablets
Metoclopramide is contraindicated: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 ) ].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 ) ]. 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 )
AND PRECAUTIONS 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 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 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. Movements may be choreoathetotic in appearance. 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 among the elderly, especially elderly women [ ], and in patients with diabetes mellitus. Due to the risk of developing TD, avoid treatment with metoclopramide for longer than 12 weeks and reduce the dosage in elderly patients [ ]. Metoclopramide 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. Movements may be choreoathetotic in appearance. 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 among the elderly, especially elderly women [ see Use in Specific Populations ( 8.5 ) ], and in patients with diabetes mellitus. Due to the risk of developing TD, avoid treatment with metoclopramide for longer than 12 weeks and reduce the dosage in elderly patients [ see Dosage and Administration ( 2.2 , 2.3 ) ]. Discontinue metoclopramide immediately in patients who develop signs and symptoms of TD. There is no known effective treatment for established cases of TD, although in some patients TD may remit, partially or completely, within several weeks to months after metoclopramide is withdrawn.Discontinue metoclopramide immediately in patients who develop signs and symptoms of TD. There is no known effective treatment for established cases of TD, although in some patients TD may remit, partially or completely, within several weeks to months after metoclopramide is withdrawn. Metoclopramide itself may suppress, or partially suppress, the signs of TD, thereby masking the underlying disease process. The effect of this symptomatic suppression upon the long-term course of TD is unknown. Metoclopramide is contraindicated in patients with a history of TD [ ]. Metoclopramide itself may suppress, or partially suppress, the signs of TD, thereby masking the underlying disease process. The effect of this symptomatic suppression upon the long-term course of TD is unknown. Metoclopramide is contraindicated in patients with a history of TD [ see Contraindications ( 4 ) ]. Avoid metoclopramide in patients receiving other drugs that are likely to cause TD (e.g., antipsychotics).
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.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).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. Avoid treatment with metoclopramide for more than 12 weeks [ see Dosage and Administration ( 2.2 , 2.3 ), Warnings and Precautions ( 5.1 ) ]. Avoid metoclopramide in patients with Parkinson’s disease and other patients being treated with antiparkinsonian drugs due to potential exacerbation of symptoms.see Dosage and Administration ( 2.2 , 2.3 ), Warnings and Precautions ( 5.1 ) 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). Avoid metoclopramide in patients receiving other drugs associated with NMS, including typical and atypical antipsychotics. 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.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.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:Management of NMS includes: Immediate discontinuation of metoclopramide and other drugs not essential to concurrent therapy [ see Drug Interactions ( 7.1 ) ]. Intensive symptomatic treatment and medical monitoring. Treatment of any concomitant serious medical problems for which specific treatments are available.
5.4 Depression Depression has occurred in metoclopramide-treated patients with and without a history of depression. Symptoms have included suicidal ideation and suicide. Avoid metoclopramide use in patients with a history of depression.
5.5 Hypertension Metoclopramide may elevate blood pressure. In one study in hypertensive patients, intravenously administered metoclopramide was shown to release catecholamines; hence, avoid use in patients with hypertension or in patients taking monoamine oxidase inhibitors [ see Drug Interactions ( 7.1 ) ]. There are also clinical reports of hypertensive crises in patients with undiagnosed pheochromocytoma. Metoclopramide is contraindicated in patients with pheochromocytoma or other catecholamine-releasing paragangliomas [ see Contraindications ( 4 ) ]. Discontinue metoclopramide in any patient with a rapid rise in blood pressure.
5.6 Fluid Retention Because metoclopramide produces a transient increase in plasma aldosterone, patients with cirrhosis or congestive heart failure may be at risk of developing fluid retention and volume overload. Discontinue metoclopramide if any of these adverse reactions occur.
5.7 Hyperprolactinemia As with other dopamine D 2 receptor antagonists, metoclopramide elevates prolactin levels. Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported with prolactin-elevating drugs, including metoclopramide. Hyperprolactinemia may potentially stimulate prolactin-dependent breast cancer. However, some clinical studies and epidemiology studies have not shown an association between administration of dopamine D 2 receptor antagonists and tumorigenesis in humans [ see Nonclinical Toxicology ( 13.1 ) ].
5.8 Effects of the Ability to Drive and Operate Machinery Metoclopramide may impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle. Concomitant use of central nervous system (CNS) depressants or drugs associated with EPS may increase this effect (e.g., alcohol, sedatives, hypnotics, opiates, and anxiolytics). Avoid metoclopramide or the interacting drug, depending on the importance of the drug to the patient [ see Drug Interactions ( 7.1 ) ].