Metoclopramide Hcl (metoclopramide HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Metoclopramide hydrochloride is a dopamine D2-receptor antagonist, an antiemetic, and a stimulant of upper GI motility (prokinetic agent).
Metoclopramide hydrochloride is a dopamine D2-receptor antagonist, an antiemetic, and a stimulant of upper GI motility (prokinetic agent). The principal pharmacologic effects of metoclopramide involve the GI tract and CNS. Although the exact mechanism of action of metoclopramide in GI disorders is unclear, it appears to sensitize tissue to the actions of acetylcholine, resulting in stimulation of the upper GI tract, without causing stimulation of gastric, biliary, or pancreatic secretions.
The activity of metoclopramide can be inhibited by anticholinergic drugs, and its effects on motility are not dependent on intact vagal innervation. Metoclopramide increases gastric contraction tone and amplitude, relaxes the pyloric sphincter and duodenal bulb, and increases peristalsis of the duodenum and jejunum. Together, these effects result in the acceleration of gastric emptying and intestinal transit.
Metoclopramide increases the resting tone of the lower esophageal sphincter, while having minimal to no effects on colon or gallbladder motility. The antiemetic effects of metoclopramide are likely due to the drug's effects on dopamine, which typically causes nausea and vomiting through stimulation of the medullary chemoreceptor trigger zone (CTZ). Metoclopramide reduces nausea and vomiting through the blockade of central and peripheral dopamine receptors, resulting in decreased stimulation of the CTZ.
Metoclopramide is rapidly and well-absorbed from the GI tract following oral administration. Relative to a 20 mg intravenous dose, the absolute bioavailability of orally administered metoclopramide is about 80%. Following administration of a single oral dose, peak plasma concentrations are attained within 1-2 hours; peak plasma concentrations are attained in a similar time frame at steady state.
Metoclopramide exposure based on AUC increases linearly for doses 20-100 mg. In a study in infants (3.5 weeks-5.4 months of age) with gastroesophageal reflux who received 0.15-mg/kg oral doses of metoclopramide every 6 hours for 10 doses as an oral solution, the mean peak plasma concentration (56.8 ng/mL) of the drug after the 10th dose was 2-fold higher compared with that after the first dose (29 ng/mL), suggesting that metoclopramide accumulates in plasma following multiple oral dosing in this age group. When administered under fasting conditions in adults, metoclopramide orally disintegrating tablets are bioequivalent to metoclopramide conventional tablets.
Administration of the orally disintegrating tablets immediately after a high-fat meal did not affect the extent of absorption, but decreased the peak blood concentration by 17%; the time to peak concentration was increased from approximately 1.8 hours when administered under fasting conditions to 3 hours when administered immediately after a high-fat meal. The clinical importance of the decrease in peak blood concentration if the orally disintegrating tablets are inadvertently administered with food is unknown. Following intranasal or IV administration of metoclopramide 10 mg, bioavailability of intranasally administered metoclopramide was 47% that of IV metoclopramide.
Absorption of the drug is reduced following intranasal administration compared with oral administration; systemic exposure (peak concentration and AUC) and time to reach peak concentration are similar following a 15-mg intranasal dose or a 10-mg oral dose. Over an intranasal dose range of 10-80 mg, exposure to the drug is proportional to dose. Metoclopramide AUC and peak concentration following intranasal administration are increased by 34 and 42%, respectively, in females compared with males.
Lean body weight (range: 34-94 kg) also appears to affect the pharmacokinetics of the intranasally administered drug, with lower systemic exposure expected in individuals with higher lean body weight. The clinical relevance of these findings is unknown. The onset of the principal pharmacologic actions of metoclopramide on the GI tract is 1-3 minutes following IV administration, 10-15 minutes following IM administration, and 30-60 minutes following oral administration.
Pharmacologic effects persist for 1-2 hours following administration of a single dose.
Metoclopramide is 30% protein bound. Metoclopramide undergoes enzymatic metabolism via oxidation as well as conjugation with glucuronic acid and sulfuric acid in the liver. Monodeethylmetoclopramide, a major oxidative metabolite, is formed mainly by cytochrome P-450 isoenzyme 2D6 (CYP2D6), an enzyme subject to genetic variability.
In adults with normal renal function, the half-life of metoclopramide ranges from 5-6 hours. A half-life of 8.1 hours has been reported following intranasal administration. In pediatric patients receiving oral or IV metoclopramide, the elimination half-life of the drug reportedly is 4.1-4.5 hours.
Following oral administration of 0.15-mg/kg doses of metoclopramide every 6 hours for 10 doses in an infant (3.5 weeks of age), elimination half-lives of 23.1 and 10.3 hours were observed after the first and tenth dose, respectively, which were substantially longer than those reported in older infants, suggesting a reduced clearance in the neonate possibly associated with immature renal and hepatic functions present at birth.
In a limited number of adults with normal renal function, approximately 85% of an oral dose of radiolabeled metoclopramide was excreted in urine within 72 hours of administration; approximately 50% of the drug excreted in urine is present as free or conjugated metoclopramide. About 18 and 22% of a 10 mg and 20 mg oral dose of metoclopramide, respectively, is excreted in urine as unchanged drug within 36 hours.
Clearance of metoclopramide is decreased, and the half-life of metoclopramide is prolonged in patients with impaired renal function. In patients with moderate or severe renal impairment (creatinine clearance <60 mL/minute), systemic exposure to metoclopramide, as measured by AUC, following oral administration is approximately 2-fold that observed in individuals with normal renal function; in those with end-stage renal disease (ESRD) requiring dialysis, systemic exposure is approximately 3.5-fold that observed in individuals with normal renal function. Metoclopramide is only minimally removed by hemodialysis or peritoneal dialysis.
In a limited number of patients with severe hepatic impairment (Child-Pugh class C), average clearance of metoclopramide following oral administration was reduced by approximately 50% compared with patients with normal hepatic function.
USES: Metoclopramide is used to prevent nausea and vomiting from surgery or chemotherapy. It is also used by people with diabetes who have slow emptying of their stomachs (gastroparesis). Treating gastroparesis can decrease symptoms of nausea, vomiting, and stomach/abdominal fullness.
Metoclopramide may also be used in certain procedures where stomach emptying is needed. Metoclopramide works by blocking a natural substance (dopamine) which can cause nausea and vomiting. It also speeds up stomach emptying and movement of the upper intestines.
This drug is not recommended for use in children younger than 1 year due to an increased risk of serious side effects (such as muscle spasms/uncontrolled muscle movements). Ask the doctor or pharmacist for details.
Generic name: metoclopramide HCl
Pronunciation: (MET-oh-KLOE-pra-mide)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Metoclopramide Hcl
Indications
The following indications are listed for Metoclopramide Hcl:
- Diabetic Gastroparesis
- Gastrointestinal Radiography Adjunct
- Intubation Of Gastrointestinal Tract
- Prevention Of Cancer Chemotherapy-Induced Nausea And Vomiting
- Prevention Of Post-Operative Nausea And Vomiting
Also known as: Adjunct Gastrointestinal Radiography, Cancer Chemotherapy-Induced N & V Prophylaxis, Diabetic Gastric Stasis, Gi Radiography Adjunct, Postop Nausea And Vomiting Prophylaxis, Postoperative Nausea And Vomiting Prophylaxis.
Dosing
Although USP currently states that potency of metoclopramide hydrochloride preparations should be expressed both in terms of the salt and the base (''active moiety''), dosage currently is expressed in terms of the base.
Therapy with metoclopramide, including all dosage forms and routes of administration, should not exceed 12 weeks' duration because of the increased risk of developing tardive dyskinesia with longer-term use.
Metoclopramide nasal spray delivers 15 mg of metoclopramide per 70-mcL metered spray. Each bottle contains 9.8 mL of solution, which is sufficient for administration 4 times daily over a period of 4 weeks.
Metoclopramide is administered orally, intranasally, by IM or direct IV injection, or by IV infusion.
Therapy with the drug, including all dosage forms and routes of administration, should not exceed 12 weeks' duration because of the risk for developing tardive dyskinesia with longer-term use. Oral and intranasal preparations of metoclopramide are recommended for adults only.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Metoclopramide undergoes oxidative metabolism via cytochrome P-450 isoenzyme 2D6 (CYP2D6), as well as conjugation with glucuronic acid and sulfuric acid.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Concomitant use of other drugs likely to cause extrapyramidal reactions.
*History of tardive dyskinesia or dystonic reaction to metoclopramide.
*Mechanical obstruction or perforation or other situations in which stimulation of GI motility might be dangerous.
*GI hemorrhage.
*Pheochromocytoma or other catecholamine-releasing paragangliomas (due to potential for hypertensive/pheochromocytoma crisis).
*History of seizure disorders.
*Known hypersensitivity to metoclopramide.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in >10% of patients receiving oral metoclopramide include restlessness, drowsiness, fatigue, and lassitude.
The most common adverse effects reported in patients receiving parenteral metoclopramide include restlessness, sleepiness, tiredness, dizziness, exhaustion, headache, confusion, and difficulty sleeping.
Adverse effects reported in >=5% of patients receiving metoclopramide nasal spray include dysgeusia, headache, and fatigue.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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The safety profile of metoclopramide in adults cannot be extrapolated to pediatric patients. Dystonias and other extrapyramidal reactions to metoclopramide are more common in pediatric patients than in adults.
Safety and efficacy of oral and intranasal formulations of metoclopramide have not been established in pediatric patients, and these formulations are not recommended for use in pediatric patients because of the risk of tardive dyskinesia and other extrapyramidal reactions, as well as the risk of methemoglobinemia in neonates.
Safety and efficacy of metoclopramide injection in pediatric patients have been established only for use to facilitate intubation of the small intestine. Metoclopramide injection should be used with caution in pediatric patients, since the incidence of extrapyramidal reactions is increased in these patients. Metoclopramide injection should be administered with caution to neonates because decreased clearance may result in increased serum concentrations of the drug. In addition, since neonates have reduced concentrations of cytochrome-b5 reductase, they may be more susceptible to methemoglobinemia.
Following oral or IV administration of metoclopramide in pediatric patients, pharmacodynamics of the drug are highly variable, and a relationship between drug plasma concentrations and pharmacodynamic effects has not been established. Data are insufficient to determine whether the pharmacokinetics of the drug in pediatric patients are similar to those in adults.
Published studies, including retrospective cohort studies, national registry studies, and meta-analyses, have not revealed an increased risk of adverse pregnancy-related outcomes with metoclopramide use during pregnancy. However, metoclopramide crosses the placenta and may cause extrapyramidal reactions and methemoglobinemia in neonates whose mothers received the drug during delivery; these neonates should be monitored for extrapyramidal effects.
Reproduction studies in pregnant rats and rabbits using metoclopramide dosages of approximately 6 and 12 times, respectively, the MRHD have not revealed evidence of adverse developmental effects.
Limited published data indicate that metoclopramide is distributed into milk; the estimated dose received by breast-fed infants is <10% of the maternal weight-adjusted oral dose. In one study, the estimated dose received by infants from breast milk ranged from 6-24 mcg/kg daily at 3-9 days postpartum and from 1-13 mcg/kg daily at 8-12 weeks postpartum. Exposure is expected to be similar following maternal doses of 10 mg administered orally or 15 mg administered intranasally. Adverse GI effects, including intestinal discomfort and increased intestinal gas formation, have been reported in breast-fed infants who were exposed to metoclopramide. Although metoclopramide increases prolactin concentrations, data are not adequate to support drug-related effects on milk production.
The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for metoclopramide and any potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition. Nursing neonates should be monitored for extrapyramidal effects (dystonias) and methemoglobinemia.
Because geriatric adults are more likely to have reduced renal function and may be more sensitive to the therapeutic or adverse effects of metoclopramide, a reduced initial dosage of the drug is recommended.
Diabetic Gastroparesis: For relief of symptoms associated with diabetic gastroparesis in geriatric patients, a reduced initial oral metoclopramide dosage of 5 mg 4 times daily, given 30 minutes before meals and at bedtime, should be considered. Dosage may be titrated to a dosage of 10 mg 4 times daily based on response and tolerability. The maximum recommended oral dosage is 40 mg daily. Metoclopramide nasal spray is not recommended as initial therapy for relief of acute and recurrent diabetic gastroparesis in geriatric patients >=65 years of age. Geriatric patients may be switched from an alternative metoclopramide preparation administered at a stable dosage of 10 mg 4 times daily to the nasal formulation administered at a dosage of 15 mg (one spray in one nostril) given 30 minutes before meals and at bedtime (maximum 4 times daily) for 2 to 8 weeks, depending on symptomatic response.
Gastroesophageal Reflux Disease: For the symptomatic treatment of gastroesophageal reflux in geriatric patients, a reduced initial oral metoclopramide dosage of 5 mg 4 times daily, given 30 minutes before meals and at bedtime, should be considered. Dosage may be titrated to a dosage of 10-15 mg 4 times daily based on response and tolerability. The maximum recommended oral dosage is 60 mg daily.
Geriatric patients are more likely to have decreased renal function and may be more sensitive to therapeutic or adverse effects of metoclopramide. Geriatric patients, especially older women, are at increased risk for tardive dyskinesia. In addition, the risk of developing parkinsonian symptoms increases with increasing dosage. Therefore, geriatric patients should receive the lowest effective dosage of metoclopramide. If parkinsonian symptoms develop in a geriatric patient receiving metoclopramide, metoclopramide generally should be discontinued before any specific antiparkinsonian therapy is considered. Sedation has been reported in patients receiving metoclopramide and may manifest as confusion and oversedation in geriatric patients.
Metoclopramide is known to be substantially eliminated by the kidneys, and the risk of adverse reactions to the drug, including tardive dyskinesia, may be increased in patients with impaired renal function. A reduced dosage should be considered in geriatric patients. In general, the dosage should be selected carefully, usually initiating therapy at the low end of the dosage range; the greater frequency of decreased renal function and of concomitant disease and drug therapy observed in geriatric patients also should be considered.
ICD codes
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Last reviewed · Source: First Databank (FDB) drug data
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