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  • CLASSES

    Other Agents for Gastric-Acid Related Disorders
    Propulsives

    DEA CLASS

    Rx

    DESCRIPTION

    Oral, parenteral, and nasal GI prokinetic agent
    Used for diabetic gastroparesis and select adults with GERD; injection helpful for PONV prevention, chemotherapy-induced emesis, and as a procedural adjunct
    Use should be kept to 12 weeks or less due to risk for tardive dyskinesia; use in pediatric patients is not recommended except for limited, short-term circumstances

    COMMON BRAND NAMES

    Metozolv, Reglan

    HOW SUPPLIED

    Metoclopramide Hydrochloride Oral Sol: 5mg, 5mL
    Metoclopramide Hydrochloride/Metozolv Oral Tab Orally Dis: 5mg, 10mg
    Metoclopramide Hydrochloride/Reglan Intramuscular Inj Sol: 1mL, 5mg
    Metoclopramide Hydrochloride/Reglan Intravenous Inj Sol: 1mL, 5mg
    Metoclopramide Hydrochloride/Reglan Oral Tab: 5mg, 10mg

    DOSAGE & INDICATIONS

    For post-operative nausea/vomiting (PONV) and post-operative nausea/vomiting (PONV) prophylaxis.
    Intravenous or Intramuscular dosage
    Adults

    10 mg IM or IV near the end of the surgical procedure. Repeat every 4 to 6 hours as necessary. If required, a 20-mg dose may be used.

    Children† and Adolescents†

    Dose regimens administered in clinical practice and studies vary and include 0.1 mg/kg/dose IV, 0.15 mg/kg/dose IV, and up to 0.25 mg/kg/dose IV for early (within 6 hours) PONV. Usual Max: 10 mg/dose IV. Repeat doses of 0.1 to 0.2 mg/kg IV (Max: 10 mg/dose IV) have been administered every 6 to 8 hours if needed. In 3 randomized, double-blind, placebo-controlled trials, metoclopramide 0.25 mg/kg/dose IV was compared to ondansetron 0.1 to 0.15 mg/kg/dose IV for PONV. In each trial, prophylactic administration of ondansetron was more effective than metoclopramide or placebo in controlling postoperative emesis. No adverse effects were reported for metoclopramide in these studies.

    For emetogenic chemotherapy-induced nausea/vomiting and chemotherapy-induced nausea/vomiting prophylaxis.
    Intravenous dosage
    Adults

    1 to 2 mg/kg IV infusion given 30 minutes before beginning chemotherapy and repeated every 2 hours for 2 doses, and then every 3 hours for 3 doses. The initial 2 doses should be 2 mg/kg/dose if highly emetogenic drugs such as cisplatin or dacarbazine are used alone or in combination. For less emetogenic regimens, 1 mg/kg/dose may suffice. Per ASCO guidelines, metoclopramide is a second-line treatment to consider for those patients not responding to the usual standard antiemetic regimens. The manufacturer does not recommend metoclopramide use longer than 12 weeks in duration.

    Children† and Adolescents†

    2 mg/kg/dose IV infusion, given 30 minutes prior to chemotherapy, then repeated at intervals 2 to 4 hours later (Max: 5 doses/day) have been used for highly emetogenic chemotherapy regimens. 1 mg/kg/dose IV infusion regimens have been used clinically for less emetogenic chemotherapy. Pretreatment with diphenhydramine has been recommended to reduce the risk for extrapyramidal side effects, which occur at a significant incidence at repeated doses of 2 mg/kg/dose IV or more. Metoclopramide is significantly less effective than serotonin 5HT3 agonists at reducing emesis, and it is less tolerable. Metoclopramide is sometimes used as a second-line antiemetic treatment.

    To facilitate intestinal intubation and for use as a diagnostic aid during gastrointestinal radiography.
    Intravenous dosage
    Adults and Adolescents 14 years or older

    10 mg IV as a single dose administered over 1 to 2 minutes.

    Children and Adolescents 6 to 14 years

    2.5 to 5 mg IV as a single dose administered over 1 to 2 minutes.

    Children younger than 6 years

    0.1 mg/kg IV as a single dose administered over 1 to 2 minutes.

    For the treatment of symptomatic gastroesophageal reflux disease (GERD).
    Oral dosage
    Adults

    10 to 15 mg PO up to 4 times per day, 30 minutes before meals and at bedtime. Geriatric patients may respond to a dose of 5 mg. For intermittent symptoms, single doses up to 20 mg prior to the provoking situation may be preferred. If the patient is a poor metabolizer of CYP2D6, the recommended dose is 5 mg PO 4 times daily or 10 mg PO 3 times daily (Max: 30 mg). Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Therapy for more than 12 weeks is not recommended. According to treatment guidelines, there is no clear role for the use of metoclopramide in the treatment of GERD. Evidence demonstrates that PPI therapy is central in the treatment of GERD symptoms. The added benefit of augmenting PPI therapy with metoclopramide has not been adequately studied. Likewise, combination therapy with metoclopramide and H2 antagonists has not been shown to be more effective than either agent used alone. In light of its safety profile, metoclopramide use in GERD should be limited.

    Children† and Adolescents†

    0.1 mg/kg/dose (Max: 10 mg/dose) PO every 6 to 8 hours is commonly used in clinical practice; limited data are available. Doses ranging from 0.1 to 0.2 mg/kg/dose PO every 6 to 8 hours have been studied. In a double-blind, randomized controlled trial of pediatric patients (aged 4 months to 17 years), metoclopramide 0.17 mg/kg/dose PO 3 times daily did not reduce the frequency or duration of GERD symptoms compared to placebo.

    Infants†

    0.1 mg/kg/dose PO every 6 to 8 hours is commonly used in clinical practice; limited data are available. Doses ranging from 0.1 to 0.2 mg/kg/dose every 6 to 8 hours have been studied. In a double-blind, placebo-controlled trial, 30 infants (aged 1 to 9 months) received metoclopramide 0.1 mg/kg/dose PO 4 times daily. There was no significant difference in GERD symptoms between the metoclopramide and placebo treatment groups, but in infants older than 3 months, the daily weight gain was greater in the metoclopramide group compared to placebo (34 +/- 8 vs. 7 +/- 11 grams/day). The percentage of time the esophageal pH was 4 or less was also significantly changed in the metocolopramide group, 10.3% vs. 13.4% of time in the metoclopramide and placebo group, respectively (p < 0.005). In a study of 18 infants (mean age 6.5 months), metoclopramide 0.2 mg/kg/dose PO 4 times daily was compared to cisapride 0.33 mg/kg/dose PO 4 times daily and placebo. Metoclopramide significantly decreased the number of reflux episodes, the percentage of time pH less than 4, and number of reflux episodes longer than 5 minutes relative to placebo (p less than 0.01). In a double-blind randomized controlled trial of pediatric patients (including a limited number of infants 4 months and older), metoclopramide 0.17 mg/kg/dose PO 3 times daily did not reduce the frequency or duration of GERD symptoms compared to placebo.

    Neonates†

    0.1 to 0.15 mg/kg/dose PO every 6 hours has been studied; limited data are available, and neonatal use is not established. In a single-dose pharmacokinetic study of 0.1 to 0.15 mg/kg in 10 premature neonates (31 to 40 weeks postconceptional age), the investigators recommended 0.15 mg/kg/dose PO based on pharmacokinetic simulations. Doses greater than 0.15 mg/kg/dose could result in increased adverse effects and should be avoided.[53599]

    Intravenous or Intramuscular dosage
    Adults

    10 mg IV or IM up to 4 times per day, 30 minutes before meals and at bedtime. Geriatric patients may respond to a dose of 5 mg. Switch to oral therapy as soon as feasible. Therapy for more than 12 weeks is not recommended. According to treatment guidelines, there is no clear role for the use of metoclopramide in the treatment of GERD. Evidence demonstrates that PPI therapy is central in the treatment of GERD symptoms. The added benefit of augmenting PPI therapy with metoclopramide has not been adequately studied. Likewise, combination therapy with metoclopramide and H2 antagonists has not been shown to be more effective than either agent used alone. In light of its safety profile, metoclopramide use in GERD should be limited.

    For the treatment of diabetic gastroparesis or postsurgical gastroparesis†.
    Oral, Intravenous, or Intramuscular dosage
    Adults

    10 mg PO, IV, or IM 4 times per day, given 30 minutes before meals and at bedtime for 2 to 8 weeks is the FDA-approved dosage in the treatment of diabetic gastroparesis. Max: 40 mg/day PO. CYP2D6 poor metabolizers require dose reduction to 5 mg 4 times daily (Max: 20 mg/day). Consider a similar lower initial dosage for geriatric patients. Avoid treatment with metoclopramide (all dosage forms and routes of administration) for more than 12 weeks because of the increased risk of tardive dyskinesia (TD) with longer-term use. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Severe symptoms may require IV/IM therapy for up to 10 days before symptoms subside. Gastroparesis treatment guidelines recommend 5 to 10 mg PO 2 to 3 times daily before meals (Max: 40 mg/day). Drug holidays or dose reductions (e.g., 5 mg, before 2 main meals of the day) should be considered whenever clinically possible.

    Nasal dosage (Gimoti nasal spray)
    Adults

    1 spray (15 mg) in 1 nostril, 30 minutes before each meal and at bedtime for 2 to 8 weeks, depending on the symptomatic response. Max: 4 sprays/day (60 mg/day). Avoid treatment with metoclopramide (all dosage forms and routes of administration) for more than 12 weeks because of the increased risk of tardive dyskinesia (TD) with longer-term use.

    Geriatric Adults

    Metoclopramide nasal spray is not recommended as initial therapy as geriatric patients may be more sensitive to the adverse effects. If already receiving an alternative metoclopramide product at 10 mg 4 times daily, the geriatric patient can be switched to the nasal spray: 1 spray (15 mg) in 1 nostril, 30 minutes before each meal and at bedtime for 2 to 8 weeks, depending on the symptomatic response. Max: 4 sprays/day (60 mg/day). Avoid treatment with metoclopramide (all dosage forms and routes of administration) for more than 12 weeks because of the increased risk of tardive dyskinesia (TD) with longer-term use.

    For the acute treatment of migraine†.
    Intravenous dosage
    Adults

    10 mg IV once. Guidelines classify metoclopramide as having probable efficacy for the treatment of acute migraine in general, while highly likely to be effective in the emergency department setting.

    Children and Adolescents

    0.1 to 0.2 mg/kg/dose (Max: 10 mg/dose) IV; may repeat dose once.

    For the treatment of persistent singultus (hiccups)†.
    Oral, Intravenous, or Intramuscular dosage
    Adults

    Metoclopramide 10 mg PO or IV/IM every 6 hours has been given for persistent or intractable hiccup. If hiccups are relieved, maintenance therapy for at least 10 days is recommended.

    For lactation induction†.
    Oral dosage
    Adult Females

    Initially, 10 mg PO 2 or 3 times daily. Dosages of 15 mg/day or lower have not been effective. The typical effective dosage range is 20 to 45 mg/day PO, administered in divided doses; do not exceed 45 mg/day because of concerns of the effects of metoclopramide on the breast-feeding infant.

    For use as a radiation sensitizer in combination with radiation therapy in the treatment of patients with non-small cell lung cancer (NSCLC)†.
    Intramuscular or Intravenous dosage
    Adults

    As a radiosensitizing agent in the treatment of non-small cell lung cancer, a dose of 2 mg/kg IV (Sensamide) was administered 1 hour prior to radiation therapy 3 times per week in a phase II/III trial.

    For the treatment of pregnancy-induced nausea/vomiting†.
    Oral dosage
    Adult pregnant females

    5 to 10 mg PO every 6 to 8 hours; limit use to the shortest possible duration. Per the American College of Gynecology and Obstetrics (ACOG) metoclopramide is a third-line pharmacologic option if symptoms persist after a trial of nonpharmacologic options and other preferred pharmacologic options (e.g., vitamin B6, doxylamine, promethazine, prochlorperazine, dimenhydrinate, diphenhydramine).

    Intravenous or Intramuscular dosage
    Adult pregnant females

    5 to 10 mg IV or IM every 6 to 8 hours; limit use to the shortest possible duration. Per the American College of Gynecology and Obstetrics (ACOG) metoclopramide is a third-line pharmacologic option if symptoms persist after a trial of nonpharmacologic options and other preferred pharmacologic options (e.g., vitamin B6, doxylamine, promethazine, prochlorperazine, dimenhydrinate, diphenhydramine).

    For the facilitation of gastric emptying in neonates with feeding intolerance†.
    Oral dosage
    Preterm and Term Neonates

    0.033 to 0.1 mg/kg/dose PO 3 times daily; data are very limited; use in neonates not established. In a small study, 6 premature neonates (birth weight 790 to 1,040 grams, gestational ages 26 to 35 weeks) received metoclopramide 0.033 mg/kg/dose IV 3 times daily at a mean postnatal age of 35 days. During metoclopramide therapy, there was a significant difference in gastric aspirate (5 +/- 2 vs. 17 +/- 5 mL/day), weight gain (25 +/- 2 vs. 15 +/- 3.7 grams/day), intestinal transit times (14 +/- 2.4 vs. 30 +/- 3 hours), and volume of feeds (110 +/- 20 vs. 45 +/- 12 mL/kg/day) compared to values before metoclopramide (p less than 0.01). In a retrospective review of 14 premature neonates (mean age 5 weeks, mean birth weight 1,100 grams, 29 weeks gestation,) who had tolerated no enteral feedings, metoclopramide 0.033 or 0.1 mg/kg/dose PO 3 times daily was administered for an average of 4 weeks. Treatment with metoclopramide decreased residual gastric volume and increased tolerance to feedings.

    Intravenous dosage
    Preterm and Term Neonates

    0.033 to 0.1 mg/kg/dose IV 3 times daily; data are very limited; use in neonates not established. In a small study, 6 premature neonates (birth weight 790 to ,1040 grams, gestational ages 26 to 35 weeks) received metoclopramide 0.033 mg/kg/dose IV 3 times daily at a mean postnatal age of 35 days. During metoclopramide therapy, there was a significant difference in gastric aspirate (5 +/- 2 vs. 17 +/- 5 mL/day), weight gain (25 +/- 2 vs. 15 +/- 3.7 grams/day), intestinal transit times (14 +/- 2.4 vs. 30 +/- 3 hours), and volume of feeds (110 +/- 20 vs. 45 +/- 12 mL/kg/day) compared to values before metoclopramide (p less than 0.01). In a retrospective review of 14 premature neonates (mean age 5 weeks, mean birth weight 1,100 grams, 29 weeks gestation,) who had tolerated no enteral feedings, metoclopramide 0.033 or 0.1 mg/kg/dose PO 3 times daily was administered for an average of 4 weeks. Treatment with metoclopramide decreased residual gastric volume and increased tolerance to feedings.

    For the treatment of Tourette's syndrome† or chronic tic disorders†.
    Oral dosage
    Children and Adolescents 6 years and older

    0.5 mg/kg/day PO, given in 3 to 4 divided doses, up to Max: 40 mg/day PO, has been used. One trial used a range of 5 to 40 mg/day, given in divided doses. Initiate at the low end of the dosage range and titrate according to tolerability and response. Use the lowest effective dose to minimize the risk of adverse effects. Metoclopramide is generally not recommended for use in pediatric patients as tardive dyskinesia (TD) and other extrapyramidal symptoms associated with metoclopramide are more common in pediatric patients than in adults. Avoid use of metoclopramide for longer than 12 weeks because of the increased risk of developing TD with longer-term use. The American Academy of Neurology practice guideline states that metoclopramide is possibly more likely than placebo to reduce tic severity in pediatric patients with Tourette's syndrome or chronic tic disorders; however, the benefits of use should outweigh the risks (e.g., increased prolactin, TD). There is insufficient evidence to determine the relative efficacy of metoclopramide to other dopamine antagonists, such as antipsychotics.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    60 mg/day or 20 mg PO, IV, or IM per single dose and 15 mg nasally per single dose; therapy for more than 12 weeks not recommended by FDA-approved product labeling.

    Geriatric

    60 mg/day or 20 mg PO, IV, or IM per single dose and 15 mg nasally per single dose; lower dosage may be sufficient in the elderly; therapy for more than 12 weeks not recommended by FDA-approved product labeling.

    Adolescents

    0.2 mg/kg/dose IV (Max: 10 mg/dose IV) and 0.2 mg/kg/dose PO (Max: 10 mg/dose or 0.8 mg/kg/day PO) have been reported; 2 mg/kg/dose IV infusion has been used for emetogenic chemotherapy.

    Children

    0.2 mg/kg/dose IV (Max: 10 mg/dose IV) and 0.2 mg/kg/dose PO (Max: 10 mg/dose or 0.8 mg/kg/day PO) have been reported; 2 mg/kg/dose IV infusion has been used for emetogenic chemotherapy.

    Infants

    0.1 mg/kg/dose IV and 0.2 mg/kg/dose PO (Max: 0.8 mg/kg/day PO) have been most commonly reported.

    Neonates

    Data are limited; safety and efficacy not established. 0.1 mg/kg/dose IV and 0.15 mg/kg/dose PO (Max: 0.6 mg/kg/day PO) have been reported.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Diabetic Gastroparesis
    Mild hepatic impairment (Child-Pugh Class A): 10 mg PO 4 times daily (Max: 40 mg/day). No dosage adjustment is recommended for metoclopramide nasal spray.
    Moderate or severe hepatic impairment (Child-Pugh Class B or C): 5 mg PO 4 times daily (Max: 20 mg/day). Metoclopramide nasal spray is not recommended in these patients.
     
    Gastroesophageal Reflux
    Mild hepatic impairment (Child-Pugh Class A): 10 to 15 mg PO 4 times daily (Max: 60 mg/day).
    Moderate or severe hepatic impairment (Child-Pugh Class B or C): 5 mg PO 4 times daily or 10 mg PO 3 times daily (Max: 30 mg/day).

    Renal Impairment

    Diabetic Gastroparesis
    CrCl more than 60 mL/minute: No adjustment is needed.
    CrCl 60 mL/minute or less: Initiate metoclopramide oral tablet at 5 mg PO 4 times daily (Max: 20 mg/day) and titrate to response. Metoclopramide nasal spray is not recommended in these patients.
    CrCl 40 mL/minute or less: Initiate metoclopramide ODT, solution, and injection at 5 mg 4 times daily (Max: 20 mg/day) and titrate to response.
     
     
    Gastroesophageal Reflux
    CrCl more than 60 mL/minute: No adjustment is needed.
    CrCl 60 mL/minute or less: Initiate metoclopramide oral tablet at 5 mg PO 4 times daily or 10 mg PO 3 times daily (Max: 30 mg/day).
    CrCl 40 mL/minute or less: Initiate metoclopramide ODT, solution, and injection at 5 mg PO 4 times daily or 10 mg PO 3 times daily (Max: 30 mg/day).
     
    Adult recommendations have also included the following renal dose adjustments :
    CrCl more than 50 mL/minute: give 100% of the normal dose.
    CrCl 10 to 50 mL/minute: give 75% of the normal dose.
    CrCl less than 10 mL/minute: give 50% of the normal dose.
     
    Pediatric recommendations have included the following renal dose adjustments :
    CrCl 30 to 50 mL/minute: give 75% of the normal dose.
    CrCl 10 to 29 mL/minute: give 50% of the normal dose.
    CrCl less than 10 mL/minute: give 25% of the normal dose.
     
    Intermittent hemodialysis:
    Hemodialysis removes relatively little metoclopramide. For oral dosages, the FDA-approved product labeling recommends 5 mg PO 4 times daily or 10 mg PO twice daily for gastroesophageal reflux and 5 mg PO twice daily for diabetic gastroparesis. Other experts have recommended the following dose recommendations for CrCl less than 10 mL/minute; no supplementation after hemodialysis is recommended in adults. A supplement of 25% of a normal dose has been recommended after a dialysis session in pediatrics. Metoclopramide nasal spray is not recommended in these patients.
     
    Continuous renal replacement therapy (CRRT):
    Follow dose recommendations for CrCl 10 to 50 mL/minute in adults. For pediatric patients, follow dose recommendations for CrCl less than 10 mL/minute; a supplement of 75% of a normal dose has been recommended after a CRRT session in pediatrics.
     
    Continuous ambulatory peritoneal dialysis (CAPD)
    Continuous ambulatory peritoneal dialysis does not remove significant amounts of the drug. For oral dosages, the FDA-approved product labeling recommends 5 mg PO 4 times daily or 10 mg PO twice daily for gastroesophageal reflux and 5 mg PO twice daily for diabetic gastroparesis. Other experts have recommended the following dose recommendations for CrCl less than 10 mL/minute. Metoclopramide nasal spray is not recommended in these patients.

    ADMINISTRATION

    Oral Administration

    Administer doses 30 minutes before each meal and at bedtime.

    Oral Solid Formulations

    Oral disintegrating tablets (Metosolv ODT):
    Remove only 1 dose from the packaging just prior to administration. If the ODT breaks or crumbles while handling, it should be discarded and a new tablet removed.
    Instruct the patient to place a tablet on the tongue, allow it to dissolve for approximately 1 minute, then swallow.
    Take the ODT without liquid.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    IV Push
    No dilution is necessary for doses 10 mg or less in adults.
    Inject over 1 to 2 minutes.
    Dosages over 10 mg should be diluted and administered as an IV infusion.
     
    Intermittent IV Infusion
    The dosage for infusion may be diluted to a concentration of 0.2 mg/mL.
    Dilute doses more than 10 mg in at least 50 mL of 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or other compatible solution such as 5% Dextrose and 0.45% Sodium Chloride Injection, Ringer's Injection, or Lactated Ringer's Injection.
    Infuse IV slowly over at least 15 minutes.
    Stability: Any of the diluted infusions are stable under normal light conditions and room temperature for up to 24 hours; or, if refrigerated and protected from light, up to 48 hours. Metoclopramide is most stable when diluted with 0.9% Sodium Chloride Injection; dilutions in 0.9% Sodium Chloride Injection may be stored frozen up to 4 weeks.

    Intramuscular Administration

    No dilution necessary.
    Inject into a large muscle mass.

    Inhalation Administration
    Intranasal Inhalation Administration

    Metoclopramide Nasal solution (i.e., Gimati nasal spray)
    Prime the pump before administering the first dose from a bottle by pressing down on the finger flange and releasing 10 sprays in the air.
    Place the spray nozzle tip under 1 nostril and have patient lean the head slightly forward so the tip of the spray nozzle is aimed away from the septum and toward the back of the nose.
    Close the other nostril with the other index finger. Gently move spray pump upwards so the tip of the nozzle is in the nostril.
    To ensure a full dose, hold the bottle upright while pressing down firmly and completely on finger flange and release while patient inhales slowly through the open nostril.
    Remove spray pump nozzle tip from the nostril and have patient exhale slowly through the mouth.
    Wipe the spray nozzle with a clean tissue.
    If uncertain that the spray entered the nose, do not repeat the dose. Administer the next dose at the scheduled time.
    To avoid contamination or the spread of infection, do not use the spray bottle for more than one person.

    STORAGE

    Generic:
    - Protect from freezing
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Metozolv:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Reglan:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Paraben hypersensitivity, procainamide hypersensitivity

    Metoclopramide should not be used in those patients with hypersensitivity to the drug or its components. Reactions have included laryngeal and glossal angioedema and bronchospasm. Since metoclopramide is structurally related to procainamide, metoclopramide should be used cautiously in patients with a known procaine or procainamide hypersensitivity due to some structural similarities with these agents. Some oral liquid preparations may contain parabens (hydroxybenzoates) and should be used with caution in patients with a known paraben hypersensitivity.

    GI bleeding, GI obstruction, GI perforation

    Metoclopramide stimulates smooth muscle in the GI tract, and use may be dangerous in certain conditions that would be aggravated by increased motility (e.g., mechanical GI obstruction, GI perforation, and GI bleeding). Metoclopramide has been used to empty the stomach of blood prior to endoscopy. Theoretically, the use of a promotility agent could place increased pressure on suture lines following surgery for gut anastomosis or closures, but such events have not been reported clinically.

    Parkinsonism, Parkinson's disease, seizure disorder, seizures, tardive dyskinesia

    Various CNS reactions, including serious movement disorders, can occur with metoclopramide therapy and may be dose-dependent and duration-dependent. Metoclopramide is contraindicated in patients with a history of tardive dyskinesia or a dystonic reaction. An FDA-required boxed warning in the prescribing information addresses the risk of tardive dyskinesia (TD) associated with high-dose or long-term use. The risk of developing TD is directly related to the length of therapy and FDA-approved labeling recommends against use for durations longer than 12 weeks. The symptoms of TD, which may include involuntary and repetitive movements of the face and body, are sometimes irreversible. Pediatric patients, patients with diabetes, and elderly patients, especially females and/or those with decreased renal function are more likely to develop TD and thus should be treated with caution. Due to the risk of developing TD and other extrapyramidal symptoms, pediatric patients should generally not receive metoclopramide, and a dosage reduction is recommended for elderly patients. If dyskinetic symptoms occur, discontinue metoclopramide. Some patients experience partial or complete remission of symptoms within several weeks of drug discontinuation, however dyskinetic movements can persist even after metoclopramide has been withdrawn. Parkinsonian-like symptoms (parkinsonism) have occurred, and while symptoms can develop at any time during therapy, they commonly occur within the first 6 months of treatment. Symptoms generally subside within 2 to 3 months after drug discontinuation. Patients with Parkinson's disease should be given metoclopramide cautiously, if at all, since such patients may experience an exacerbation of motor symptoms when taking metoclopramide. Extrapyramidal symptoms have also been reported and manifest as acute dystonic reactions usually occurring in the first 24 to 48 hours of treatment; symptoms generally disappear within 24 hours of drug discontinuation. Metoclopramide should not be used in patients with a seizure disorder (or acute seizures) or in patients receiving drugs that are likely to cause extrapyramidal reactions, since the frequency and severity of seizures or extrapyramidal reactions may be increased. Extrapyramidal symptoms are dose-dependent and occur more frequently in pediatric patients and adult patients under the age of 30.

    Children, infants, methemoglobin reductase deficiency, methemoglobinemia, neonates

    Children and infants are more likely to experience extrapyramidal effects from metoclopramide. Intravenous metoclopramide is FDA-approved for use in pediatric patients to facilitate small bowel intubation; oral metoclopramide is not FDA-approved for any indication in pediatrics, although oral administration has been used off-label in pediatric patients for certain indications. Metoclopramide nasal spray is not recommended in pediatric patients less than 18 years of age due to the risk of developing tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates. Safety data in adults cannot be extrapolated to the pediatric population. Care should be exercised in administering metoclopramide to neonates since prolonged clearance may produce excessive serum concentrations; European product labels for metoclopramide contraindicate the drug's use in neonates, though metoclopramide has not been explicitly contraindicated for neonatal use in U.S. product labels. Neonates have reduced levels of NADH-cytochrome b5 reductase (methemoglobin reductase deficiency) and this deficiency makes neonates more susceptible to methemoglobinemia. Methylene blue has been administered in pediatric patients without G6PD deficiency for reversal of methemoglobinemia, however, methylene blue treatment may cause hemolytic anemia and is not recommended in patients with G6PD deficiency who experience metoclopramide-induced methemoglobinemia.

    Cardiac disease, heart failure, hypertension, pheochromocytoma

    Because metoclopramide produces a transient increase in plasma aldosterone, certain patients, especially those with congestive heart failure, may be at risk of developing fluid retention and volume overload. If these side effects occur at any time during metoclopramide therapy, the drug should be discontinued. Caution is also recommended in patients with existing hypertension or cardiac disease that may be sensitive to catecholamine release. Metoclopramide is contraindicated in patients with pheochromocytoma because it can stimulate the release of catecholamines, possibly leading to a hypertensive crisis.

    Abrupt discontinuation, depression, driving or operating machinery

    Various CNS reactions can occur with metoclopramide therapy and may be dose-dependent. Avoid the use of injectable, oral, and nasal metoclopramide chronically in patients with a history of depression; use only when the expected benefits of therapy outweigh the potential risks. Reported symptoms in patients with and without a history of depression have ranged from mild to severe, and include suicidal ideation and suicide. Inform the patient or their caregiver that metoclopramide can cause drowsiness or dizziness, or otherwise impair mental and/or physical abilities. Patients should not perform activities requiring coordination and concentration, such as driving or operating machinery, until they are aware of how metoclopramide affects them. A small number of patients may experience discontinuation symptoms, such as dizziness, nervousness, and/or headaches following abrupt discontinuation of metoclopramide. A slower taper when stopping metoclopramide may be appropriate for some patients, although this is not typically recommended.

    Hepatic disease, poor metabolizers

    Metoclopramide clearance is reduced in patients with hepatic disease. Oral or parenteral dosage adjustments are required in patients with moderate or severe hepatic impairment (Child-Pugh B or C). The use of metoclopramide nasal spray is not recommended in patients with moderate to severe hepatic disease. Metoclopramide's metabolite is formed primarily by CYP2D6, an enzyme subject to genetic variability. Patients who are CYP2D6 poor metabolizers (CYP2D6 PMs) have reduced clearance of metoclopramide and require oral and parenteral dose reductions. The use of metoclopramide nasal spray is not recommended in CYP2D6 poor metabolizers. Because metoclopramide produces a transient increase in plasma aldosterone, certain patients, especially those with hepatic cirrhosis, may be at risk of developing fluid retention and volume overload. If these side effects occur at any time during metoclopramide therapy, the drug should be discontinued.

    Renal failure, renal impairment

    Metoclopramide should be used with caution in patients with renal impairment and renal failure, due to possible accumulation and toxicity. Reduced initial oral and parenteral doses are recommended for patients with reduced creatinine clearance. Metoclopramide nasal spray is not recommended in patients with moderate or severe renal impairment.

    Breast cancer, hyperprolactinemia, infertility

    Metoclopramide stimulates the release of prolactin and may cause hyperprolactinemia. Some human breast cancer may be prolactin-dependent and therefore metoclopramide should be used extremely cautiously in patients who have a history of breast cancer. Neither clinical or epidemiological evidence to date has supported an association between metoclopramide use and breast cancer. Because metoclopramide stimulates the release of prolactin, it may induce infertility secondary to hyperprolactinemia in some men or women or may induce other endocrine abnormalities.

    Pregnancy

    Available data with metoclopramide use in pregnancy is insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Currently available animal and human data do not support an association between the use of metoclopramide in pregnancy and congenital defects. No controlled human gestation studies are available; use during pregnancy only if necessary. Chronic use (e.g., greater than 12 weeks) should be avoided due to the increased risk for the development of movement disorders such as tardive dyskinesia. Metoclopramide has been used off-label as an adjunct, based on risk-benefit ratios, for the treatment of severe nausea/vomiting of pregnancy (e.g., hyperemesis gravidarium) not responding to standard treaements. The American College of Obstetricians and Gynecologists (ACOG) guidelines include metoclopramide as a third-line pharmacologic treatment option for nausea/vomiting of pregnancy in patients who have failed other therapies; limit use to the shortest duration possible. A retrospective cohort study compared infants exposed to metoclopramide through maternal use during the first trimester (n = 3,458) to infants who were not exposed to metoclopramide (n = 78,245) and found no significant differences in major congenital malformations, birth weight, preterm delivery, or perinatal death. Placental transfer of metoclopramide in most stages of pregnancy is unknown; however, IV doses given just prior to cesarean section have been associated with placental transfer at term, with umbilical venous to maternal plasma concentration ratios of approximately 0.6. Doses given during labor do not appear to have effects on fetal prolactin secretion or other hormones.

    Breast-feeding

    Limited published data report the presence of metoclopramide in human milk in variable amounts. Historically, metoclopramide was recommended to be used with caution in breast-feeding mothers secondary to the potential for CNS effects in the infant from the use of the drug. Based on clinical use, maternal doses up to 10 mg orally 3 times per day, which translates to roughly a 1 to 45 mcg/kg/day ingestion in the infant, do not appear to pose a significant risk to the breast-feeding infant. The estimated ingestions are much lower than the oral dosages an infant would receive in therapeutic administration (i.e., 100 to 800 mcg/kg/day). Metoclopramide has been used off-label to stimulate the release of prolactin from the anterior pituitary, thus increasing lactation in women with inadequate or decreased milk production in dosages of 20 to 45 mg/day orally. Two studies, 1 in mothers of premature infants and 1 in mothers who experienced complete or partial lactation failure, showed no significant difference in breast milk volume, duration of breast-feeding, weight gain, or reduction in the amount of supplemental milk in infants whose mothers were treated with metoclopramide versus those who were not. Both studies employed education regarding optimal breast-feeding for all of the mothers. The Academy of Breast-feeding Medicine does not recommend any specific pharmacologic galactagogue based on inconclusive evidence of their efficacy and the risk of side effects in both mothers and their infants. In summary, dosages below 45 mg/day in the lactating woman are probably not harmful to the infant, but the drug should be used only when the benefit to the mother outweighs the potential risk to the infant.

    Geriatric

    Geriatric patients should receive the lowest dose of metoclopramide that is effective. The elderly are more at risk for side effects such as tardive dyskinesia, confusion or oversedation, and parkinsonian-like side effects. The risk of developing parkinsonian-like side effects increases with ascending dose. If parkinsonian-like symptoms develop in a geriatric patient receiving metoclopramide, the drug should generally be discontinued before initiating any specific anti-parkinsonian agents. According to the Beers Criteria, metoclopramide is considered a potentially inappropriate medication (PIM) in geriatric patients and should be avoided due to the risk of extrapyramidal effects, including tardive dyskinesia, which may be increased in frail older adults and with prolonged exposure. The Beers panel also recommends avoiding dopamine receptor antagonists such as metoclopramide in geriatric patients with Parkinson's disease because of the potential for symptom exacerbation. The Beers expert panel considers the treatment of gastroparesis (not to exceed 12 weeks with rare exception) as an acceptable use for metoclopramide in the elderly. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs); metoclopramide is considered a high-risk medication with limited clinical indications and effectiveness. Metoclopramide is not recommended for first-line gastroesophageal reflux disease (GERD) treatment. When used for diabetic gastroparesis or other indications, evaluate and document benefits vs. risks for the patient. Metoclopramide may cause restlessness, drowsiness, insomnia, depression, distress, anorexia, lowering of the seizure threshold, or extrapyramidal symptoms; these adverse consequences are of particular concern in older adults. Closely monitor at-risk patients for adverse effects.

    Malignant hyperthermia

    Rare occurrences of neuroleptic malignant syndrome (NMS) have been reported during metoclopramide therapy. This potentially fatal syndrome is comprised of the symptom complex of malignant hyperthermia, altered consciousness, muscular rigidity, and autonomic dysfunction (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac arrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Immediately evaluate patients who present with these symptoms. 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. Treatment of NMS includes immediate discontinuation of metoclopramide and other drugs not essential to concurrent therapy, intensive symptomatic treatment and medical monitoring, and treatment of any concomitant serious medical problems for which specific treatments are available.

    ADVERSE REACTIONS

    Severe

    seizures / Delayed / Incidence not known
    suicidal ideation / Delayed / Incidence not known
    torticollis / Delayed / Incidence not known
    laryngospasm / Rapid / Incidence not known
    tardive dyskinesia / Delayed / Incidence not known
    AV block / Early / Incidence not known
    heart failure / Delayed / Incidence not known
    bradycardia / Rapid / Incidence not known
    hepatotoxicity / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    methemoglobinemia / Early / Incidence not known
    bronchospasm / Rapid / Incidence not known
    laryngeal edema / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    porphyria / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    serotonin syndrome / Delayed / Incidence not known
    neuroleptic malignant syndrome / Delayed / Incidence not known

    Moderate

    dystonic reaction / Delayed / 0.2-0.2
    depression / Delayed / Incidence not known
    confusion / Early / Incidence not known
    hallucinations / Early / Incidence not known
    dyspnea / Early / Incidence not known
    trismus / Delayed / Incidence not known
    akathisia / Delayed / Incidence not known
    pseudoparkinsonism / Delayed / Incidence not known
    involuntary movements / Delayed / Incidence not known
    galactorrhea / Delayed / Incidence not known
    hyperprolactinemia / Delayed / Incidence not known
    infertility / Delayed / Incidence not known
    impotence (erectile dysfunction) / Delayed / Incidence not known
    edema / Delayed / Incidence not known
    hypertension / Early / Incidence not known
    supraventricular tachycardia (SVT) / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    fluid retention / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    urinary incontinence / Early / Incidence not known
    neutropenia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    withdrawal / Early / Incidence not known

    Mild

    dysgeusia / Early / 15.0-15.0
    fatigue / Early / 10.0-10.0
    drowsiness / Early / 10.0-10.0
    restlessness / Early / 10.0-10.0
    nausea / Early / 4.0-6.0
    headache / Early / 4.0-5.0
    dizziness / Early / 1.0-4.0
    vomiting / Early / 2.0-2.0
    diarrhea / Early / Incidence not known
    insomnia / Early / Incidence not known
    tremor / Early / Incidence not known
    amenorrhea / Delayed / Incidence not known
    menstrual irregularity / Delayed / Incidence not known
    gynecomastia / Delayed / Incidence not known
    breast enlargement / Delayed / Incidence not known
    urinary urgency / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    rash / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Metoclopramide can increase the rate or extent of absorption of aspirin because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Codeine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Minor) Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.
    Acetaminophen; Hydrocodone: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Oxycodone: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Alfentanil: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Alosetron: (Moderate) Although a potential interaction has not been studied, metoclopramide might negate the effect of alosetron. Pharmacodynamic interactions between alosetron and drugs that enhance peristalsis are theoretically possible, based on opposing pharmacologic outcomes. It may be prudent to avoid use of metoclopramide during alosetron treatment.
    Amantadine: (Major) Metoclopramide is a central dopamine antagonist and can antagonize the actions of dopamine agonists such as amantadine. In addition, metoclopramide may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, tardive dyskinesia), and rarely, neuroleptic malignant syndrome. The manufacturer of metoclopramide does not specifically contraindicate the use of metoclopramide and dopamine agonists; however, coadministration should be avoided if possible.
    Amiloride; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Amlodipine; Celecoxib: (Moderate) A dosage adjustment may be warranted for metoclopramide if coadministered with celecoxib due to the potential for celecoxib to enhance the exposure and toxicity of metoclopramide. Celecoxib is a CYP2D6 inhibitor, and metoclopramide is a CYP2D6 substrate.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Amoxapine: (Major) Metoclopramide is a central dopamine antagonist and may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, or tardive dyskinesia), and rarely, neuroleptic malignant syndrome. Metoclopramide is contraindicated with other drugs that are likely to cause extrapyramidal effects since the risk of these effects may be increased. Case reports and case series have implicated tricyclic antidepressants in causing a variety of extrapyramidal symptoms (EPS). Although the occurrence is infrequent compared to antipsychotic-induced EPS, the risk of these events may be increased during concurrent use of metoclopramide and tricyclic antidepressants compared to monotherapy with either agent. The related cyclic compound amoxapine has significant anti-dopaminergic properties, and several cases of EPS have been reported during use of this drug. It is advisable to avoid coadministration of metoclopramide and amoxapine if possible.
    Anticholinergics: (Moderate) Drugs with significant antimuscarinic activity, such as anticholinergics and antimuscarinics, may slow GI motility and thus may reduce the prokinetic actions of metoclopramide. Monitor patients for an increase in gastrointestinal complaints, such as reflux or constipation. Additive drowsiness may occur as well. The clinical significance is uncertain.
    Anxiolytics; Sedatives; and Hypnotics: (Minor) Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.
    Apomorphine: (Moderate) Agents with dopamine antagonist properties, like metoclopramide, may decrease the effectiveness of dopamine agonists. These agents can cause abrupt and severe worsening of Parkinson's disease or restless leg syndrome (RLS) symptoms. Metoclopramide should be avoided, if possible, in patients treated with dopamine agonists for Parkinson's disease. If not avoidable, monitor for reduced efficacy of the dopamine agonist. Additive somnolence may also be possible.
    Aripiprazole: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Artemether; Lumefantrine: (Major) Due to the risk of increased metoclopramide plasma concentrations and extrapyramidal adverse reactions, dose adjustments of oral metoclopramide are recommended when administered in combination with strong CYP2D6 inhibitors. In patients with gastroesophageal reflux receiving a strong CYP2D6 inhibitor or who are known CYP2D6 poor metabolizers (PMs), the recommended dose of metoclopramide is 5 mg PO four times daily or 10 mg PO three times daily. In patients with diabetic gastroparesis receiving a strong CYP2D6 inhibitor or who are known CYP2D6 poor metabolizers (PMs), the recommended dose of metoclopramide is 5 mg PO four times daily times daily. Metoclopramide is a substrate of CYP2D6 and lumefantrine is a strong CYP2D6 inhibitor.
    Articaine; Epinephrine: (Moderate) Coadministration of articaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue articaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Asenapine: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Aspirin, ASA: (Minor) Metoclopramide can increase the rate or extent of absorption of aspirin because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Aspirin, ASA; Butalbital; Caffeine: (Minor) Metoclopramide can increase the rate or extent of absorption of aspirin because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Minor) Metoclopramide can increase the rate or extent of absorption of aspirin because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Aspirin, ASA; Caffeine: (Minor) Metoclopramide can increase the rate or extent of absorption of aspirin because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Minor) Metoclopramide can increase the rate or extent of absorption of aspirin because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Metoclopramide can increase the rate or extent of absorption of aspirin because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Aspirin, ASA; Carisoprodol: (Minor) Metoclopramide can increase the rate or extent of absorption of aspirin because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Minor) Metoclopramide can increase the rate or extent of absorption of aspirin because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Metoclopramide can increase the rate or extent of absorption of aspirin because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Aspirin, ASA; Dipyridamole: (Minor) Metoclopramide can increase the rate or extent of absorption of aspirin because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Aspirin, ASA; Omeprazole: (Minor) Metoclopramide can increase the rate or extent of absorption of aspirin because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Aspirin, ASA; Oxycodone: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Minor) Metoclopramide can increase the rate or extent of absorption of aspirin because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Aspirin, ASA; Pravastatin: (Minor) Metoclopramide can increase the rate or extent of absorption of aspirin because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Atazanavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with metoclopramide as there is a potential for elevated metoclopramide and cobicistat concentrations. Metoclopramide is a CYP2D6 substrate/inhibitor and cobicistat is a substrate/inhibitor of CYP2D6.
    Atenolol; Chlorthalidone: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Atovaquone: (Major) Avoid the concomitant use of metoclopramide and atovaquone. Metoclopramide may reduce the bioavailability of atovaquone. Use metoclopramide with atovaquone only if other antiemetics are not available.
    Atovaquone; Proguanil: (Major) Avoid the concomitant use of metoclopramide and atovaquone. Metoclopramide may reduce the bioavailability of atovaquone. Use metoclopramide with atovaquone only if other antiemetics are not available.
    Atropine; Difenoxin: (Moderate) Diphenoxylate/difenoxin decreases GI motility. Diphenoxylate/difenoxin may antagonize the muscarinic and/or prokinetic effects of other drugs, including metoclopramide.
    atypical antipsychotic: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Azilsartan; Chlorthalidone: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Barbiturates: (Minor) Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.
    Belladonna; Opium: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Benazepril; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Bendroflumethiazide; Nadolol: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Benzhydrocodone; Acetaminophen: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Benzodiazepines: (Minor) Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Minor) Metoclopramide can increase the rate or extent of absorption of tetracycline because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Metoclopramide can increase the rate or extent of absorption of tetracycline because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Brexpiprazole: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Bromocriptine: (Major) Metoclopramide is a central dopamine antagonist. Metoclopramide can antagonize the actions of dopamine agonists such as bromocriptine; therefore, the combined use of these agents is not recommended.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Bupivacaine Liposomal: (Moderate) Coadministration of bupivacaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Bupivacaine: (Moderate) Coadministration of bupivacaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Bupivacaine; Lidocaine: (Moderate) Coadministration of bupivacaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Coadministration of lidocaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Bupivacaine; Meloxicam: (Moderate) Coadministration of bupivacaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Bupropion: (Major) When metoclopramide is used with a potent CYP2D6 inhibitor for the treatment of gastroesophageal reflux (GERD), dosage reductions of oral metoclopramide are required, with maximum oral dosage not to exceed 30 mg/day (e.g., 5 mg 4 times daily or 10 mg 3 times daily). There is a known increase in metoclopramide exposure and an increased risk for extrapyramidal adverse reactions. Metoclopramide is a substrate of CYP2D6 and bupropion is a strong CYP2D6 inhibitor. The manufacturer recommends avoidance of bupropion when oral metoclopramide is used in patients with diabetic gastroparesis. Healthy patients given 20 mg of metoclopramide and a potent CYP2D6 inhibitor for 8 days had a 40% and 90% increase in metoclopramide Cmax and AUC, respectively, compared to patients who received metoclopramide alone.
    Bupropion; Naltrexone: (Major) When metoclopramide is used with a potent CYP2D6 inhibitor for the treatment of gastroesophageal reflux (GERD), dosage reductions of oral metoclopramide are required, with maximum oral dosage not to exceed 30 mg/day (e.g., 5 mg 4 times daily or 10 mg 3 times daily). There is a known increase in metoclopramide exposure and an increased risk for extrapyramidal adverse reactions. Metoclopramide is a substrate of CYP2D6 and bupropion is a strong CYP2D6 inhibitor. The manufacturer recommends avoidance of bupropion when oral metoclopramide is used in patients with diabetic gastroparesis. Healthy patients given 20 mg of metoclopramide and a potent CYP2D6 inhibitor for 8 days had a 40% and 90% increase in metoclopramide Cmax and AUC, respectively, compared to patients who received metoclopramide alone.
    Buspirone: (Minor) Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Cabergoline: (Moderate) Cabergoline should not be coadministered with metoclopramide. The prolactin-lowering effect of cabergoline may be diminished by medications that increase prolactin levels such as metoclopramide. Metoclopramide increases prolactin levels through central dopamine blockade while cabergoline decreases prolactin levels through dopamine agonist effects.
    Candesartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and metoclopramide. CNS depressants can potentiate the effects of cannabidiol.
    Captopril; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Carbidopa; Levodopa: (Major) Metoclopramide is a central dopamine antagonist. Metoclopramide can antagonize the actions of dopamine agonists such as levodopa. In addition, metoclopramide may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, tardive dyskinesia), and rarely, neuroleptic malignant syndrome. Dyskinesias and other extrapyramidal effects have been reported during treatment with various anti-parkinson's medications, particularly levodopa. A symptom complex resembling neuroleptic malignant syndrome in association with rapid dose reduction, withdrawal of, or changes in anti-parkinsonian therapy has also been observed. The manufacturer of metoclopramide does not specifically contraindicate the use of metoclopramide and dopamine agonists; however, coadministration should be avoided if possible.
    Carbidopa; Levodopa; Entacapone: (Major) Metoclopramide is a central dopamine antagonist. Metoclopramide can antagonize the actions of dopamine agonists such as levodopa. In addition, metoclopramide may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, tardive dyskinesia), and rarely, neuroleptic malignant syndrome. Dyskinesias and other extrapyramidal effects have been reported during treatment with various anti-parkinson's medications, particularly levodopa. A symptom complex resembling neuroleptic malignant syndrome in association with rapid dose reduction, withdrawal of, or changes in anti-parkinsonian therapy has also been observed. The manufacturer of metoclopramide does not specifically contraindicate the use of metoclopramide and dopamine agonists; however, coadministration should be avoided if possible. (Moderate) Coadministration of COMT inhibitors and metoclopramide should be avoided if possible. Metoclopramide may interfere with the effectiveness of COMT inhibitors. Metoclopramide has dopamine antagonist properties while COMT inhibitors increase the availability of catecholamine concentrations (e.g., dopamine) in the central nervous system.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Cariprazine: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Celecoxib: (Moderate) A dosage adjustment may be warranted for metoclopramide if coadministered with celecoxib due to the potential for celecoxib to enhance the exposure and toxicity of metoclopramide. Celecoxib is a CYP2D6 inhibitor, and metoclopramide is a CYP2D6 substrate.
    Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and metoclopramide. Concurrent use may result in additive CNS depression.
    Chloral Hydrate: (Minor) Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.
    Chloroprocaine: (Moderate) Coadministration of chloroprocaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Chlorothiazide: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Chlorpheniramine; Codeine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Hydrocodone: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorthalidone: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Chlorthalidone; Clonidine: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Cinacalcet: (Major) Due to the risk of increased metoclopramide plasma concentrations and extrapyramidal adverse reactions, dose adjustments of oral metoclopramide are recommended when administered in combination with strong CYP2D6 inhibitors. In patients with gastroesophageal reflux receiving a strong CYP2D6 inhibitor, the recommended dose of metoclopramide is 5 mg PO four times daily or 10 mg PO three times daily. In patients with diabetic gastroparesis receiving a strong CYP2D6 inhibitor, the recommended dose of metoclopramide is 5 mg PO four times daily times daily. Metoclopramide is a substrate of CYP2D6 and cinacalcet is a strong CYP2D6 inhibitor.
    Ciprofloxacin: (Minor) Metoclopramide accelerates the absorption of oral ciprofloxacin. This results in shorter time to reach maximum ciprofloxacin plasma concentrations. No effect was seen on the bioavailability of ciprofloxacin.
    Clozapine: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with metoclopramide as there is a potential for elevated metoclopramide and cobicistat concentrations. Metoclopramide is a CYP2D6 substrate/inhibitor and cobicistat is a substrate/inhibitor of CYP2D6.
    Codeine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Guaifenesin: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Phenylephrine; Promethazine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Promethazine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    COMT inhibitors: (Moderate) Coadministration of COMT inhibitors and metoclopramide should be avoided if possible. Metoclopramide may interfere with the effectiveness of COMT inhibitors. Metoclopramide has dopamine antagonist properties while COMT inhibitors increase the availability of catecholamine concentrations (e.g., dopamine) in the central nervous system.
    Cyclosporine: (Moderate) Monitor cyclosporine concentrations and adjust the dose as needed if concomitant use of metoclopramide is necessary. Metoclopramide alters gastric motility resulting in increased absorption of cyclosporine.
    Dacomitinib: (Major) Dose adjustments of oral metoclopramide are recommended when administered in combination with dacomitinib due to the risk of increased metoclopramide plasma concentrations and extrapyramidal adverse reactions. In patients with diabetic gastroparesis, avoid coadministration with dacomitinib. If coadministration cannot be avoided, the recommended dose of metoclopramide is 5 mg PO four times daily. In patients with gastroesophageal reflux, the recommended dose of metoclopramide is 5 mg PO four times daily or 10 mg PO three times daily when coadministered with dacomitinib. Metoclopramide is a substrate of CYP2D6 and dacomitinib is a strong CYP2D6 inhibitor. Coadministration with another strong CYP2D6 inhibitor increased the metoclopramide Cmax and AUC by 40% and 90%, respectively.
    Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with metoclopramide as there is a potential for elevated metoclopramide and cobicistat concentrations. Metoclopramide is a CYP2D6 substrate/inhibitor and cobicistat is a substrate/inhibitor of CYP2D6.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is warranted when cobicistat is administered with metoclopramide as there is a potential for elevated metoclopramide and cobicistat concentrations. Metoclopramide is a CYP2D6 substrate/inhibitor and cobicistat is a substrate/inhibitor of CYP2D6.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of metoclopramide with ritonavir may result in elevated plasma concentrations of metoclopramide. Metoclopromide is metabolized by the hepatic isoenzyme CYP2D6; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Degarelix: (Major) Avoid coadministration of degarelix with metoclopramide due to the risk of reduced efficacy of degarelix. Metoclopramide can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; degarelix is a GnRH analog.
    Deutetrabenazine: (Moderate) Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and metoclopramide is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Concurrent use of deutetrabenazine and drugs that cause CNS depression, such as metoclopramide, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Dextromethorphan; Quinidine: (Major) Dose reductions of oral metoclopramide are recommended when administered in combination with quinidine due to likely increased metoclopramide exposure and an increased risk of extrapyramidal adverse reactions. In patients with diabetic gastroparesis, avoid coadministration of metoclopramide with quinidine. If coadministration cannot be avoided, the recommended dose of metoclopramide is 5 mg PO four times daily times daily. In patients with gastroesophageal reflux, the recommended dose of metoclopramide is 5 mg PO four times daily or 10 mg PO three times daily when coadministered with quinidine. Metoclopramide is a substrate of CYP2D6 and quinidine is a strong CYP2D6 inhibitor. Coadministration with another strong CYP2D6 inhibitor increased the metoclopramide Cmax and AUC by 40% and 90%, respectively.
    Digoxin: (Moderate) Digoxin absorption and bioavailability may be diminished in some patients on metoclopramide due to the increased rate of transit from the stomach, where digoxin is normally absorbed. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of metoclopramide. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Diphenoxylate; Atropine: (Moderate) Diphenoxylate/difenoxin decreases GI motility. Diphenoxylate/difenoxin may antagonize the muscarinic and/or prokinetic effects of other drugs, including metoclopramide.
    dopamine agonists: (Moderate) Agents with dopamine antagonist properties, like metoclopramide, may decrease the effectiveness of dopamine agonists. These agents can cause abrupt and severe worsening of Parkinson's disease or restless leg syndrome (RLS) symptoms. Metoclopramide should be avoided, if possible, in patients treated with dopamine agonists for Parkinson's disease. If not avoidable, monitor for reduced efficacy of the dopamine agonist. Additive somnolence may also be possible.
    Droperidol: (Major) Avoid droperidol in patients receiving metoclopramide due to potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Both drugs are associated with extrapyramidal symptoms and rarely, neuroleptic malignant syndrome. Additive sedation is also possible.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with metoclopramide as there is a potential for elevated metoclopramide and cobicistat concentrations. Metoclopramide is a CYP2D6 substrate/inhibitor and cobicistat is a substrate/inhibitor of CYP2D6.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with metoclopramide as there is a potential for elevated metoclopramide and cobicistat concentrations. Metoclopramide is a CYP2D6 substrate/inhibitor and cobicistat is a substrate/inhibitor of CYP2D6.
    Enalapril; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Entacapone: (Moderate) Coadministration of COMT inhibitors and metoclopramide should be avoided if possible. Metoclopramide may interfere with the effectiveness of COMT inhibitors. Metoclopramide has dopamine antagonist properties while COMT inhibitors increase the availability of catecholamine concentrations (e.g., dopamine) in the central nervous system.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Esketamine: (Moderate) Closely monitor patients receiving esketamine and metoclopramide for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
    Eszopiclone: (Minor) Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.
    Ethanol: (Moderate) Concurrent use of ethanol can increase the CNS depressant effects of metoclopramide.
    Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and metoclopramide. Concurrent use may result in additive CNS depression.
    Fenoldopam: (Moderate) Metoclopramide or other peripherally acting dopamine antagonists may inhibit the blood pressure effects of fenoldopam. In one in vitro study, the vasodilatory response to fenoldopam was attenuated by pretreatment with metoclopramide, a nonselective dopamine antagonist.
    Fentanyl: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Fluoxetine: (Major) When metoclopramide is used with a potent CYP2D6 inhibitor for the treatment of gastroesophageal reflux (GERD), dosage reductions of oral metoclopramide are required, with maximum oral dosage not to exceed 30 mg/day (e.g., 5 mg 4 times daily or 10 mg 3 times daily). There is a known increase in metoclopramide exposure and an increased risk for extrapyramidal adverse reactions. Metoclopramide is a substrate of CYP2D6 and fluoxetine is a strong CYP2D6 inhibitor. The manufacturer recommends avoidance of fluoxetine and consideration of alternative SSRI antidepressants when oral metoclopramide is used in patients with diabetic gastroparesis. Healthy patients given 20 mg of metoclopramide and 60 mg of fluoxetine for 8 days had a 40% and 90% increase in metoclopramide Cmax and AUC, respectively, compared to patients who received metoclopramide alone.
    Fosfomycin: (Moderate) When coadministered with fosfomycin, metoclopramide, a drug which increases gastrointestinal motility, lowers the serum concentration and urinary excretion of fosfomycin. Other drugs that increase gastrointestinal motility may produce similar effects. Monitor for evidence of clinical effectiveness of fosfomycin. Since fosfomycin is given as a single dose, separating times of administration may limit the interaction.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of metoclopramide and gabapentin. Concurrent use may result in additive CNS depression.
    Goserelin: (Major) Avoid coadministration of goserelin with metoclopramide due to the risk of reduced efficacy of goserelin. Metoclopramide can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog.
    Guaifenesin; Hydrocodone: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Haloperidol: (Contraindicated) Avoid metoclopramide in patients receiving haloperidol. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Histrelin: (Major) Avoid coadministration of histrelin with metoclopramide due to the risk of reduced efficacy of histrelin. Metoclopramide can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog.
    Homatropine; Hydrocodone: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Hydrochlorothiazide, HCTZ; Moexipril: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Hydrocodone: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Ibuprofen: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Phenylephrine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Pseudoephedrine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking metoclopramide. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydromorphone: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Ibuprofen; Oxycodone: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Iloperidone: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Insulins: (Moderate) Increased GI motility by metoclopramide may increase delivery of food to the intestines and increase blood glucose. The dosing of insulin may require adjustment in patients who receive metoclopramide concomitantly.
    Ipecac: (Major) Ipecac has been shown to be effective in producing emesis in patients who have ingested antiemetics, provided ipecac is given promptly (usually within 1 hour of antiemetic consumption). If ipecac is administered after antiemetic therapy has begun to exert therapeutic effects, ipecac may be less effective. It is suggested the irritating GI effects of ipecac lead to emesis following antiemetic consumption.
    Irbesartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Isocarboxazid: (Moderate) Because metoclopramide causes release of catecholamines in patients with essential hypertension, it should be administered cautiously to patients receiving MAOIs.
    Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and metoclopramide. Concurrent use may result in additive CNS depression.
    Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and metoclopramide. Dosage adjustments of lemborexant and metoclopramide may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
    Leuprolide: (Major) Avoid coadministration of leuprolide with metoclopramide due to the risk of reduced efficacy of leuprolide. Metoclopramide can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Leuprolide; Norethindrone: (Major) Avoid coadministration of leuprolide with metoclopramide due to the risk of reduced efficacy of leuprolide. Metoclopramide can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Levodopa: (Major) Metoclopramide is a central dopamine antagonist. Metoclopramide can antagonize the actions of dopamine agonists such as levodopa. In addition, metoclopramide may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, tardive dyskinesia), and rarely, neuroleptic malignant syndrome. Dyskinesias and other extrapyramidal effects have been reported during treatment with various anti-parkinson's medications, particularly levodopa. A symptom complex resembling neuroleptic malignant syndrome in association with rapid dose reduction, withdrawal of, or changes in anti-parkinsonian therapy has also been observed. The manufacturer of metoclopramide does not specifically contraindicate the use of metoclopramide and dopamine agonists; however, coadministration should be avoided if possible.
    Levorphanol: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Lidocaine: (Moderate) Coadministration of lidocaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Lidocaine; Prilocaine: (Moderate) Coadministration of lidocaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Coadministration of prilocaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Linezolid: (Major) Because metoclopramide causes release of catecholamines in patients with essential hypertension, it should be administered cautiously to patients receiving MAOIs or drugs that possess MAOI-like activity, such as linezolid.
    Lisinopril; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Loperamide: (Major) Pharmacodynamic interactions between loperamide and drugs that enhance peristalsis are theoretically possible. It is wise to avoid use loperamide in patients who metoclopramide.
    Loperamide; Simethicone: (Major) Pharmacodynamic interactions between loperamide and drugs that enhance peristalsis are theoretically possible. It is wise to avoid use loperamide in patients who metoclopramide.
    Lopinavir; Ritonavir: (Moderate) Concurrent administration of metoclopramide with ritonavir may result in elevated plasma concentrations of metoclopramide. Metoclopromide is metabolized by the hepatic isoenzyme CYP2D6; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Losartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Loxapine: (Contraindicated) Avoid metoclopramide in patients receiving loxapine. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Lumateperone: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Lurasidone: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Meperidine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Meperidine; Promethazine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Mepivacaine: (Moderate) Coadministration of mepivacaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue mepivacaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen
    Mepivacaine; Levonordefrin: (Moderate) Coadministration of mepivacaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue mepivacaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen
    Meprobamate: (Minor) Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.
    Methadone: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Methyclothiazide: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Methylphenidate Derivatives: (Moderate) In theory, metoclopramide and methylphenidate derivatives may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Patients receiving this combination should be monitored for loss of effectiveness of either agent. Methylphenidate derivatives blocks central dopamine reuptake, which increases central dopaminergic functioning, while metoclopramide is a dopamine antagonist.
    Metolazone: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Metyrosine: (Major) Metoclopramide is a central dopamine antagonist and may cause extrapyramidal reactions such as acute dystonic reactions, pseudo-parkinsonism, akathisia, or tardive dyskinesia. Metyrosine decreases the endogenous production of catecholamines. Metyrosine precipitates extrapyramidal symptoms in approximately 10% of patients receiving the drug. The manufacturer of metoclopramide does not specifically contraindicate the use of metoclopramide and metyrosine; however, coadministration should be avoided if possible.
    Mivacurium: (Moderate) Consider reducing the dose of mivacurium when metoclopramide is given concomitantly. Concomitant use of mivacurium and metoclopramide may prolong neuromuscular blockade, possibly due to plasma cholinesterase inhibition by metoclopramide.
    Molindone: (Contraindicated) Avoid metoclopramide in patients receiving molindone. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Morphine: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Morphine; Naltrexone: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Nabilone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of nabilone and metoclopramide. Concurrent use may result in additive CNS depression.
    Olanzapine: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Olanzapine; Fluoxetine: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia. (Major) When metoclopramide is used with a potent CYP2D6 inhibitor for the treatment of gastroesophageal reflux (GERD), dosage reductions of oral metoclopramide are required, with maximum oral dosage not to exceed 30 mg/day (e.g., 5 mg 4 times daily or 10 mg 3 times daily). There is a known increase in metoclopramide exposure and an increased risk for extrapyramidal adverse reactions. Metoclopramide is a substrate of CYP2D6 and fluoxetine is a strong CYP2D6 inhibitor. The manufacturer recommends avoidance of fluoxetine and consideration of alternative SSRI antidepressants when oral metoclopramide is used in patients with diabetic gastroparesis. Healthy patients given 20 mg of metoclopramide and 60 mg of fluoxetine for 8 days had a 40% and 90% increase in metoclopramide Cmax and AUC, respectively, compared to patients who received metoclopramide alone.
    Olanzapine; Samidorphan: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Oliceridine: (Moderate) Concomitant use of oliceridine with metoclopramide may cause excessive sedation and somnolence. Limit the use of oliceridine with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Olmesartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of metoclopramide with ritonavir may result in elevated plasma concentrations of metoclopramide. Metoclopromide is metabolized by the hepatic isoenzyme CYP2D6; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Opicapone: (Moderate) Coadministration of COMT inhibitors and metoclopramide should be avoided if possible. Metoclopramide may interfere with the effectiveness of COMT inhibitors. Metoclopramide has dopamine antagonist properties while COMT inhibitors increase the availability of catecholamine concentrations (e.g., dopamine) in the central nervous system.
    Oritavancin: (Moderate) Metoclopramide is metabolized by CYP2D6; oritavancin is a weak CYP2D6 inducer. Plasma concentrations and efficacy of metoclopramide may be reduced if these drugs are administered concurrently.
    Oxycodone: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Oxymorphone: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Paliperidone: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Paroxetine: (Major) When metoclopramide is used with a potent CYP2D6 inhibitor for the treatment of gastroesophageal reflux (GERD), dosage reductions of oral metoclopramide are required, with maximum oral dosage not to exceed 30 mg/day (e.g., 5 mg 4 times daily or 10 mg 3 times daily). There is a known increase in metoclopramide exposure and an increased risk for extrapyramidal adverse reactions. Metoclopramide is a substrate of CYP2D6 and paroxetine is a strong CYP2D6 inhibitor. The manufacturer recommends avoidance of paroxetine and consideration of alternative SSRI antidepressants when oral metoclopramide is used in patients with diabetic gastroparesis. Healthy patients given 20 mg of metoclopramide and a strong CYP2D6 inhibitor for 8 days had a 40% and 90% increase in metoclopramide Cmax and AUC, respectively, compared to patients who received metoclopramide alone.
    Peginterferon Alfa-2b: (Moderate) Monitor for adverse effects associated with increased exposure to metoclopramide if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while metoclopramide is a CYP2D6 substrate.
    Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue procaine and any other agents that may cause methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue procaine and any other agents that may cause methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Pergolide: (Moderate) Agents with dopamine antagonist properties, like metoclopramide, may decrease the effectiveness of dopamine agonists. These agents can cause abrupt and severe worsening of Parkinson's disease or restless leg syndrome (RLS) symptoms. Metoclopramide should be avoided, if possible, in patients treated with dopamine agonists for Parkinson's disease. If not avoidable, monitor for reduced efficacy of the dopamine agonist. Additive somnolence may also be possible.
    Phenelzine: (Moderate) Because metoclopramide causes release of catecholamines in patients with essential hypertension, it should be administered cautiously to patients receiving MAOIs.
    Phenothiazines: (Contraindicated) Avoid metoclopramide in patients receiving phenothiazine antipsychotics due to potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Also avoid the use of metoclopramide with phenothiazine antiemetics if possible due to these risks. Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. Discontinue these medications at the first signs of dyskinesia. Metoclopramide is a central dopamine antagonist and may cause EPS (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, tardive dyskinesia). Tardive dyskinesia (TD) is 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. Phenothiazines are also central dopamine antagonists. In addition, both phenothiazines and metoclopramide can cause sedation, seizures, or increased prolactin levels.
    Pimozide: (Contraindicated) Avoid metoclopramide in patients receiving pimozide. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Posaconazole: (Major) Avoid coadministration of metoclopramide with posaconazole immediate-release oral suspension unless the benefits outweigh the risks of decreased posaconazole efficacy. If used in combination, closely monitor for breakthrough fungal infections. The pharmacokinetics of posaconazole delayed-release tablets and oral suspension are not significantly affected by metoclopramide. Metoclopramide increases gastric motility resulting in decreased posaconazole absorption and lower posaconazole plasma concentrations. When a single 400 mg dose of posaconazole oral suspension was administered with metoclopramide (10 mg PO three times daily for 2 days), the mean reductions in Cmax were 21% and the mean reductions in AUC were 19% for posaconazole.
    Pramipexole: (Moderate) Agents with dopamine antagonist properties, like metoclopramide, may decrease the effectiveness of dopamine agonists. These agents can cause abrupt and severe worsening of Parkinson's disease or restless leg syndrome (RLS) symptoms. Metoclopramide should be avoided, if possible, in patients treated with dopamine agonists for Parkinson's disease. If not avoidable, monitor for reduced efficacy of the dopamine agonist. Additive somnolence may also be possible.
    Pramlintide: (Minor) Drugs that stimulate GI motility could antagonize the effects of pramlintide. Furthermore, the effects of pramlintide on patients with gastroparesis or those requiring drugs used to stimulate GI motility are not certain. Pramlintide slows gastric emptying and the rate of nutrient delivery to the small intestine. This combination has not been studied. Monitor blood glucose closely.
    Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of metoclopramide and pregabalin. Concurrent use may result in additive CNS depression.
    Prilocaine: (Moderate) Coadministration of prilocaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Prilocaine; Epinephrine: (Moderate) Coadministration of prilocaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Propranolol; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Quetiapine: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Quinapril; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Quinidine: (Major) Dose reductions of oral metoclopramide are recommended when administered in combination with quinidine due to likely increased metoclopramide exposure and an increased risk of extrapyramidal adverse reactions. In patients with diabetic gastroparesis, avoid coadministration of metoclopramide with quinidine. If coadministration cannot be avoided, the recommended dose of metoclopramide is 5 mg PO four times daily times daily. In patients with gastroesophageal reflux, the recommended dose of metoclopramide is 5 mg PO four times daily or 10 mg PO three times daily when coadministered with quinidine. Metoclopramide is a substrate of CYP2D6 and quinidine is a strong CYP2D6 inhibitor. Coadministration with another strong CYP2D6 inhibitor increased the metoclopramide Cmax and AUC by 40% and 90%, respectively.
    Ramelteon: (Minor) Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.
    Rasagiline: (Major) Close monitoring is advisable if combination therapy is necessary. The risk of extrapyramidal effects may be increased during concurrent use of metoclopramide and rasagiline, and the therapeutic benefits of rasagiline in treating Parkinson's disease may be diminished during use of a central dopamine antagonist such as metoclopramide. In addition, because metoclopramide causes release of catecholamines in patients with essential hypertension, it should be administered cautiously to patients receiving MAOIs. Rasagiline is a selective MAO-B inhibitor at manufacturer recommended doses; therefore, serious interactions with medications affecting catecholamine release are theoretically less likely.
    Remifentanil: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Risperidone: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Ritonavir: (Moderate) Concurrent administration of metoclopramide with ritonavir may result in elevated plasma concentrations of metoclopramide. Metoclopromide is metabolized by the hepatic isoenzyme CYP2D6; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Rivastigmine: (Major) Metoclopramide is a central dopamine antagonist and may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, or tardive dyskinesia), and rarely, neuroleptic malignant syndrome. Metoclopramide is contraindicated with other drugs that are likely to cause extrapyramidal effects since the risk of these effects may be increased. Cholinomimetics such as rivastigmine may cause or worsen extrapyramidal symptoms such as pseudoparkinsonism, dyskinesia, and dystonia, although the incidences of these effects during clinical trials with rivastigmine were infrequent. The risk of extrapyramidal effects may be increased during concurrent use of metoclopramide and rivastigmine; close monitoring is advisable if combination therapy is necessary.
    Ropinirole: (Moderate) Agents with dopamine antagonist properties, like metoclopramide, may decrease the effectiveness of dopamine agonists. These agents can cause abrupt and severe worsening of Parkinson's disease or restless leg syndrome (RLS) symptoms. Metoclopramide should be avoided, if possible, in patients treated with dopamine agonists for Parkinson's disease. If not avoidable, monitor for reduced efficacy of the dopamine agonist. Additive somnolence may also be possible.
    Ropivacaine: (Moderate) Coadministration of ropivacaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Rotigotine: (Major) The concurrent use of rotigotine, a dopamine agonist, and antiemetic agents with dopamine antagonist properties may decrease the effectiveness of either agent. Abrupt and severe worsening of Parkinson's disease symptoms can occur. In addition, sedation caused by the individual agents can be potentiated with combined use. Metoclopramide should be avoided if possible in patients treated with rotigotine.
    Safinamide: (Major) The concurrent use of safinamide and metoclopramide should be avoided if possible. The beneficial effects of safinamide are mediated by monoamine oxidase inhibitor type B activity which increases central dopamine availability and metoclopramide is a dopamine antagonist. In addition, metoclopramide may cause extrapyramidal effects, including pseudoparkinsonism. If these agents must be used together, monitor for exacerbation of Parkinson's disease symptoms.
    Sedating H1-blockers: (Minor) Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.
    Selegiline: (Major) Close monitoring is advisable if combination therapy is necessary. Metoclopramide is a central dopamine antagonist and may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, or tardive dyskinesia), and rarely, neuroleptic malignant syndrome. The risk of extrapyramidal effects may be increased during concurrent use of metoclopramide and selegiline, and the therapeutic benefits of selegiline in treating Parkinson's disease may be diminished during use of a central dopamine antagonist such as metoclopramide. In addition, because metoclopramide causes release of catecholamines in patients with essential hypertension, it should be administered cautiously to patients receiving MAOIs.
    Sertraline: (Moderate) Patients receiving sertraline and metoclopramide should be monitored for the emergence of extrapyramidal symptoms or other metoclopramide-related adverse effects. Increased plasma concentrations of metoclopramide may occur when metoclopramide is administered with CYP2D6 inhibitors such as sertraline, which may increase the risk of exacerbation of extrapyramidal symptoms. While sertraline does not as potently inhibit CYP2D6 as certain other SSRIs, the drug may cause significant increases in CYP2D6 substrates with narrow therapeutic indexes. It may be advisable to consider a metoclopramide dosage reduction.
    Sirolimus: (Major) Increased sirolimus whole blood concentrations may be observed if gastrointestinal prokinetic agents like metoclopramide are added to therapy. Monitor sirolimus serum concentrations carefully if a GI prokinetic agent is used concomitantly.
    Spironolactone; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Succinylcholine: (Moderate) Consider reducing the dose of succinylcholine when metoclopramide is given concomitantly. Concomitant use of succinylcholine and metoclopramide may prolong neuromuscular blockade, possibly due to plasma cholinesterase inhibition by metoclopramide.
    Sufentanil: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Tacrine: (Major) Metoclopramide is a central dopamine antagonist and may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, or tardive dyskinesia), and rarely, neuroleptic malignant syndrome. Metoclopramide is contraindicated with other drugs that are likely to cause extrapyramidal effects since the risk of these effects may be increased. Cholinomimetics such as tacrine may cause or worsen extrapyramidal symptoms such as pseudoparkinsonism, dyskinesia, and dystonia. During clinical trials, unspecified movement disorders and extrapyramidal syndrome were reported infrequently, and dystonia, tardive dyskinesia, akathisia, and facial dyskinesia occurred rarely. The risk of extrapyramidal effects may be increased during concurrent use of metoclopramide and tacrine; close monitoring is advisable if combination therapy is necessary.
    Tacrolimus: (Major) Increased tacrolimus whole blood concentrations may be observed if a GI prokinetic agent like metoclopramide is added to therapy. Monitor tacrolimus serum concentrations carefully if a GI prokinetic agent is used concomitantly.
    Tapentadol: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Tedizolid: (Moderate) Because metoclopramide causes release of catecholamines in patients with essential hypertension, it should be administered cautiously to patients receiving MAOIs or drugs that possess MAOI-like activity, such as tedizolid, a weak reversible, non-selective inhibitor of MAO.
    Telmisartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Terbinafine: (Major) Metoclopramide is a substrate of CYP2D6 and terbinafine is a strong CYP2D6 inhibitor; due to the risk of increased metoclopramide plasma concentrations and extrapyramidal adverse reactions, dose adjustments of oral metoclopramide are recommended when administered in combination with strong CYP2D6 inhibitors. In patients with gastroesophageal reflux receiving a strong CYP2D6 inhibitor or who are known CYP2D6 poor metabolizers (PMs), the recommended dose of metoclopramide is 5 mg PO four times daily or 10 mg PO three times daily. In patients with diabetic gastroparesis receiving a strong CYP2D6 inhibitor or who are known CYP2D6 poor metabolizers (PMs), the recommended dose of metoclopramide is 5 mg PO four times daily times daily.
    Tetrabenazine: (Major) Metoclopramide is a central dopamine antagonist and may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, or tardive dyskinesia), and rarely, neuroleptic malignant syndrome. Metoclopramide is contraindicated with other drugs that are likely to cause extrapyramidal effects since the risk of these effects may be increased. Tetrabenazine is a centrally-acting dopamine depleting drug. Pseudoparkinsonism (6 to12%) and akathisia (9%) were among the most frequently reported side effects during clinical trials with tetrabenazine. Neuroleptic malignant syndrome and acute dystonic reactions have also been noted rarely. The manufacturer of metoclopramide does not specifically contraindicate the use of metoclopramide and tetrabenazine; however, concurrent use should be avoided if possible.
    Tetracaine: (Moderate) Coadministration of tetracaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue tetracaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Tetracycline: (Minor) Metoclopramide can increase the rate or extent of absorption of tetracycline because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Thiazide diuretics: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Thiothixene: (Contraindicated) Avoid metoclopramide in patients receiving thiothixene due to potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. Discontinue these medications at the first signs of dyskinesia. In addition, both drugs may cause sedation, seizures, or increased prolactin levels.
    Tipranavir: (Major) Due to the risk of increased metoclopramide plasma concentrations and extrapyramidal adverse reactions, dose adjustments of oral metoclopramide are recommended when administered in combination with strong CYP2D6 inhibitors. In patients with gastroesophageal reflux receiving a strong CYP2D6 inhibitor, the recommended dose of metoclopramide is 5 mg PO four times daily or 10 mg PO three times daily. In patients with diabetic gastroparesis receiving a strong CYP2D6 inhibitor, the recommended dose of metoclopramide is 5 mg PO four times daily times daily. Metoclopramide is a substrate of CYP2D6 and tipranavir is a strong CYP2D6 inhibitor.
    Tolcapone: (Moderate) Coadministration of COMT inhibitors and metoclopramide should be avoided if possible. Metoclopramide may interfere with the effectiveness of COMT inhibitors. Metoclopramide has dopamine antagonist properties while COMT inhibitors increase the availability of catecholamine concentrations (e.g., dopamine) in the central nervous system.
    Tramadol: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Tramadol; Acetaminophen: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Tranylcypromine: (Moderate) Because metoclopramide causes release of catecholamines in patients with essential hypertension, it should be administered cautiously to patients receiving MAOIs.
    Triamterene; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Triptorelin: (Major) Avoid coadministration of triptorelin with metoclopramide due to the risk of reduced efficacy of triptorelin. Metoclopramide can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic.
    Zalcitabine, ddC: (Minor) The coadministration of zalcitabine and metoclopramide appears to result in a slight reduction in zalcitabine bioavailability, by approximately 10%. The effect is mild and no changes in dosage are suggested.
    Zaleplon: (Minor) Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.
    Ziprasidone: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
    Zolpidem: (Minor) Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.

    PREGNANCY AND LACTATION

    Pregnancy

    Available data with metoclopramide use in pregnancy is insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Currently available animal and human data do not support an association between the use of metoclopramide in pregnancy and congenital defects. No controlled human gestation studies are available; use during pregnancy only if necessary. Chronic use (e.g., greater than 12 weeks) should be avoided due to the increased risk for the development of movement disorders such as tardive dyskinesia. Metoclopramide has been used off-label as an adjunct, based on risk-benefit ratios, for the treatment of severe nausea/vomiting of pregnancy (e.g., hyperemesis gravidarium) not responding to standard treaements. The American College of Obstetricians and Gynecologists (ACOG) guidelines include metoclopramide as a third-line pharmacologic treatment option for nausea/vomiting of pregnancy in patients who have failed other therapies; limit use to the shortest duration possible. A retrospective cohort study compared infants exposed to metoclopramide through maternal use during the first trimester (n = 3,458) to infants who were not exposed to metoclopramide (n = 78,245) and found no significant differences in major congenital malformations, birth weight, preterm delivery, or perinatal death. Placental transfer of metoclopramide in most stages of pregnancy is unknown; however, IV doses given just prior to cesarean section have been associated with placental transfer at term, with umbilical venous to maternal plasma concentration ratios of approximately 0.6. Doses given during labor do not appear to have effects on fetal prolactin secretion or other hormones.

    Limited published data report the presence of metoclopramide in human milk in variable amounts. Historically, metoclopramide was recommended to be used with caution in breast-feeding mothers secondary to the potential for CNS effects in the infant from the use of the drug. Based on clinical use, maternal doses up to 10 mg orally 3 times per day, which translates to roughly a 1 to 45 mcg/kg/day ingestion in the infant, do not appear to pose a significant risk to the breast-feeding infant. The estimated ingestions are much lower than the oral dosages an infant would receive in therapeutic administration (i.e., 100 to 800 mcg/kg/day). Metoclopramide has been used off-label to stimulate the release of prolactin from the anterior pituitary, thus increasing lactation in women with inadequate or decreased milk production in dosages of 20 to 45 mg/day orally. Two studies, 1 in mothers of premature infants and 1 in mothers who experienced complete or partial lactation failure, showed no significant difference in breast milk volume, duration of breast-feeding, weight gain, or reduction in the amount of supplemental milk in infants whose mothers were treated with metoclopramide versus those who were not. Both studies employed education regarding optimal breast-feeding for all of the mothers. The Academy of Breast-feeding Medicine does not recommend any specific pharmacologic galactagogue based on inconclusive evidence of their efficacy and the risk of side effects in both mothers and their infants. In summary, dosages below 45 mg/day in the lactating woman are probably not harmful to the infant, but the drug should be used only when the benefit to the mother outweighs the potential risk to the infant.

    MECHANISM OF ACTION

    Metoclopramide's mechanism of action is complex. Unlike bethanechol, metoclopramide enhances gastric motility without stimulating gastric secretions. Peripherally, metoclopramide augments cholinergic activity either by causing the release of acetylcholine from postganglionic nerve endings or by sensitizing muscarinic receptors on smooth muscle. Vagotomy does not inhibit metoclopramide effects on the GI tract as much as pretreatment with atropine does. Further confounding the issue is the fact that high doses of metoclopramide depress the mechanical activity of GI smooth muscle, while low doses stimulate it. Effects on the resting tone of the lower esophageal sphincter combined with increased gastric emptying reduce gastroesophageal reflux, although this benefit is greater during the day than at night. The net effect of metoclopramide is the coordination of gastric and duodenal motility.
     
    Centrally, metoclopramide blocks dopaminergic receptors, specifically, the D2 receptor subtype, in the chemoreceptor trigger zone as do other clinically useful antinauseants such as prochlorperazine. Unlike the phenothiazines, however, metoclopramide does not possess antipsychotic or tranquilizing activity. Metoclopramide also appears to be less sedating than other central dopamine antagonists. Metoclopramide effectively antagonizes the actions of apomorphine, a known central dopamine agonist. Antiemetic effects of metoclopramide are mainly the result of central dopamine antagonism and increased gastric motility, however, metoclopramide also possesses weak 5-HT3 (e.g., serotonin type 3) receptor antagonism. The discovery of this minor action of metoclopramide led to the development of potent 5-HT3 antagonists such as ondansetron and granisetron. Central dopaminergic blockade produces antiemesis but also sedation and extrapyramidal effects. Inhibition of dopamine receptors in the pituitary and hypothalamus increases prolactin secretion, which can produce other adverse effects. Metoclopramide also acts on adrenal tissue to increase the secretion of aldosterone.

    PHARMACOKINETICS

    Metoclopramide is administered orally, parenterally, and intranasally. Metoclopramide is distributed into breast milk, and it crosses the blood-brain barrier and the placenta. Metoclopramide is only weakly bound to plasma protein (about 30%). The volume of distribution is approximately 3.5 L/kg, suggesting extensive distribution to body tissues. Metoclopramide undergoes enzymatic metabolism via oxidation as well as glucuronide and sulfate conjugation reactions in the liver. Monodeethylmetoclopramide, a major oxidative metabolite, is formed primarily by CYP2D6, an enzyme subject to genetic variability. Plasma concentrations decline in a biphasic manner, with a half-life of about 5 minutes in the initial phase and 2.5 to 6 hours in the terminal phase. Within 72 hours, approximately 85% of a dose is excreted in the urine as unchanged drug (20%) or as the glucuronide or sulfate in patients with normal renal function, and about 5% of an oral dose is excreted in the feces via the bile.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP2D6
    Metoclopramide is a substrate of the CYP2D6. Those patients who are CYP2D6 poor metabolizers (CYP2D6 PMs) require dose reductions, as well as patients who are receiving strong CYP2D6 inhibitors. Although in vitro studies suggest that metoclopramide can inhibit CYP2D6, metoclopramide is unlikely to interact with CYP2D6 substrates in vivo at therapeutically relevant concentrations.

    Oral Route

    Metoclopramide is rapidly and well absorbed; oral bioavailability is approximately 80% +/- 15.5% relative to intravenous dosing. Onset of action is 30 to 60 minutes after oral dosing. In the absence of gastroparesis, metoclopramide is rapidly absorbed from the GI tract. Peak plasma levels are generally achieved within 2 hours after oral dosing. Metoclopramide orally disintegrating tablets (ODT) were found to be bioequivalent to metoclopramide tablets.

    Intravenous Route

    Metoclopramide's onset of action is 1 to 3 minutes after IV injection.

    Intramuscular Route

    Metoclopramide's onset of action is 10 to 15 minutes after IM injection.

    Other Route(s)

    Intranasal Route
    The absolute bioavailability of metoclopramide following nasal administration of metoclopramide 10 mg is 47% in healthy subjects compared to intravenous injection of metoclopramide 10 mg. The systemic absorption after nasal administration is lower than that after oral administration given the same dose. Following nasal administration of metoclopramide 15 mg in healthy subjects, the systemic exposure (Cmax and AUC) to metoclopramide and the time to reach Cmax (Tmax) were similar to orally administered 10 mg metoclopramide tablet. After a single nasal administration of metoclopramide at doses ranging from 10 mg to 80 mg in healthy subjects, there was a dose-proportional increase in the mean values for Cmax and AUC.