Side Effects of Reglan (metoclopramide)

Reglan (metoclopramide) is a "prokinetic" drug that stimulates the muscles of the gastrointestinal tract including the muscles of the lower esophageal sphincter, stomach, and small intestine by interacting with receptors for acetylcholine and dopamine on gastrointestinal muscles and nerves used to treat heartburn and esophagitis due to GERD in patients with gastroparesis.

Reglan is also prescribed to treat impaired function of muscles of the small intestine and nausea due to surgery or cancer chemotherapy.

In patients with gastroesophageal reflux disease (GERD), a weakened lower esophageal sphincter allows reflux of stomach acid into the esophagus, causing heartburn and damage to the esophagus (esophagitis).

Reglan decreases the reflux of stomach acid by strengthening the muscle of the lower esophageal sphincter. Reglan also stimulates the muscles of the stomach and hastens emptying of solid and liquid meals from the stomach and into the intestines.

In some patients, particularly those with diabetes, damage to nerves in the stomach can interfere with function of the muscles and cause delayed emptying of the stomach, resulting in nausea, vomiting, a sense of abdominal fullness and distention, and heartburn (diabetic gastroparesis).

Reglan can relieve symptoms related to diabetic gastroparesis by stimulating more rapid emptying of the stomach as well as decreasing the reflux of stomach acid into the esophagus. Dopamine receptors on nerves in the brain are important in producing nausea. Reglan interacts with the dopamine receptors in the brain and can be effective in treating nausea. 

Common side effects of Reglan include

• drowsiness,
• restlessness,
• fatigue,
• anxiety,
• insomnia,
• depression, and
• sedation.

Reglan may impair the mental and/or physical abilities to drive or operate machinery.

Serious side effects of Reglan include serious neurological symptoms that mimic Parkinson's disease such as

• involuntary muscle movements,
• facial grimacing, and
• dystonic reactions resembling tetanus. 

Drug interactions of Reglan include other drugs that are absorbed in the small intestine, because Reglan accelerates emptying of the stomach, it can increase or decrease absorption and effects of these drugs. For example, the effects of alcohol, diazepam, and cyclosporine can be accelerated when used together with Reglan.

• Conversely, Reglan may decrease the concentrations in blood of digoxin and cimetidine.
• Reglan should not be used in patients taking monoamine oxidase inhibitors (MAOIs) because of the risk of serious adverse effects due to excess release of neurotransmitters.
• Concurrent administration of anticholinergic drugs can decrease the effectiveness of Reglan.

The safety of Reglan in pregnancy has not been established. Reglan is excreted in breast milk. Breastfeeding mothers should avoid Reglan.

Metoclopramide is generally well-tolerated when used in low doses for brief periods. Neurological side effects increase with higher doses and longer periods of treatment. Common side effects of metoclopramide are:

• drowsiness,
• restlessness,
• fatigue,
• anxiety,
• insomnia,
• depression,
• and sedation.

Other important side effects of metoclopramide include serious neurological symptoms that mimic Parkinson's disease such as:

• involuntary muscle movements,
• facial grimacing, and
• dystonic reactions resembling tetanus.

Fortunately, these more serious side effects are infrequent and usually - though not always - disappear when metoclopramide is discontinued. Patients with Parkinson's disease can experience worsening of symptoms with metoclopramide. Metoclopramide may impair the mental and/or physical abilities to drive or operate machinery.

In general, the incidence of adverse reactions correlates with the dose and duration of metoclopramide administration. The following reactions have been reported, although in most instances, data do not permit an estimate of frequency:

CNS Effects

Restlessness, drowsiness, fatigue, and lassitude occur in approximately 10% of patients receiving the most commonly prescribed dosage of 10 mg q.i.d. Insomnia, headache, confusion, dizziness, or mental depression with suicidal ideation occur less frequently. The incidence of drowsiness is greater at higher doses. There are isolated reports of convulsive seizures without clear-cut relationship to metoclopramide. Rarely, hallucinations have been reported.

Extrapyramidal Reactions (EPS)

Acute dystonic reactions, the most common type of EPS associated with metoclopramide, occur in approximately 0.2% of patients (1 in 500) treated with 30 to 40 mg of metoclopramide per day. Symptoms include involuntary movements of limbs, facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech, trismus, opisthotonus (tetanus-like reactions), and, rarely, stridor and dyspnea possibly due to laryngospasm; ordinarily these symptoms are readily reversed by diphenhydramine.

Parkinsonian-like symptoms may include bradykinesia, tremor, cogwheel rigidity, mask-like facies.

Tardive dyskinesia most frequently is characterized by involuntary movements of the tongue, face, mouth, or jaw, and sometimes by involuntary movements of the trunk and/or extremities; movements may be choreoathetotic in appearance.

Motor restlessness (akathisia) may consist of feelings of anxiety, agitation, jitteriness, and insomnia, as well as inability to sit still, pacing, foot tapping. These symptoms may disappear spontaneously or respond to a reduction in dosage.

Neuroleptic Malignant Syndrome

Rare occurrences of neuroleptic malignant syndrome (NMS) have been reported. This potentially fatal syndrome is comprised of the symptom complex of hyperthermia, altered consciousness, muscular rigidity, and autonomic dysfunction.

Endocrine Disturbances

Galactorrhea, amenorrhea, gynecomastia, impotence secondary to hyperprolactinemia. Fluid retention secondary to transient elevation of aldosterone.

Cardiovascular

Hypotension, hypertension, supraventricular tachycardia, bradycardia, fluid retention, acute congestive heart failure and possible AV block.

Gastrointestinal

Nausea and bowel disturbances, primarily diarrhea.

Hepatic

Rarely, cases of hepatotoxicity, characterized by such findings as jaundice and altered liver function tests, when metoclopramide was administered with other drugs with known hepatotoxic potential.

Renal

Urinary frequency and incontinence.

Hematologic

A few cases of neutropenia, leukopenia, or agranulocytosis, generally without clear-cut relationship to metoclopramide. Methemoglobinemia, in adults and especially with overdosage in neonates. Sulfhemoglobinemia in adults.

Allergic Reactions

A few cases of rash, urticaria, or bronchospasm, especially in patients with a history of asthma. Rarely, angioneurotic edema, including glossal or laryngeal edema.

Miscellaneous

Visual disturbances. Porphyria.

The effects of metoclopramide on gastrointestinal motility are antagonized by anticholinergic drugs and narcotic analgesics. Additive sedative effects can occur when metoclopramide is given with alcohol, sedatives, hypnotics, narcotics, or tranquilizers.

The finding that metoclopramide releases catecholamines in patients with essential hypertension suggests that it should be used cautiously, if at all, in patients receiving monoamine oxidase inhibitors.

Absorption of drugs from the stomach may be diminished (e.g., digoxin) by metoclopramide, whereas the rate and/or extent of absorption of drugs from the small bowel may be increased (e.g., acetaminophen, tetracycline, levodopa, ethanol, cyclosporine).

Gastroparesis (gastric stasis) may be responsible for poor diabetic control in some patients. Exogenously administered insulin may begin to act before food has left the stomach and lead to hypoglycemia. Because the action of metoclopramide will influence the delivery of food to the intestines and thus the rate of absorption, insulin dosage or timing of dosage may require adjustment.