Domperidone (Systemic)


VA CLASSIFICATION
Primary: AU300
Secondary: GA609

Commonly used brand name(s): Motilium.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.



Category:


Antiemetic—

dopaminergic blocking agent—

Indications

Accepted

Gastritis, chronic and subacute (treatment)—Domperidone is indicated for treating symptoms associated with upper gastrointestinal motility disorders caused by chronic and subacute gastritis{01}

Gastroparesis, diabetic (treatment)—Domperidone is indicated for treating symptoms associated with upper gastrointestinal motility disorders caused by diabetic gastroparesis{01}

Gastrointestinal symptoms due to dopamine agonist therapy (prophylaxis) —Domperidone is indicated to prevent gastrointestinal symptoms associated with the use of dopamine agonist antiparkinsonian agents{01}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Domperidone is structurally related to butyrophenones{01}

Mechanism of action/Effect:

Dopaminergic blocking agents—Gastrointestinal emptying (delayed) adjunct; peristaltic stimulant: The gastroprokinetic properties of domperidone are related to its peripheral dopamine receptor blocking properties. Domperidone facilitates gastric emptying and decreases small bowel transit time by increasing esophageal and gastric peristalsis and by lowering esophageal sphincter pressure.{01}

Antiemetic—The antiemetic properties of dopamine are related to its dopamine receptor blocking activity at both the chemoreceptor trigger zone and at the gastric level.{01}


Other actions/effects:

Domperidone elevates serum prolactin concentrations.{01}

Absorption:

Rapid{01}

Distribution:

Low concentrations of domperidone are found in breast milk{01}

Does not readily cross the blood-brain barrier.{01}

Protein binding:

Very high (91% to 93% ){01}

Biotransformation:

Domperidone undergoes first-pass and gut-wall metabolism. Through hydroxylation and oxidative N-dealkylation, domperidone is metabolized to hydroxydomperidone and 2,3-dihydro-2-oxo-1-H-benzimidazol-1-propionic acid, respectively.{01}

Half-life:

Elimination—7 hours after single oral and intramuscular administration.{01}

Time to peak concentration:

10 to 30 minutes following intramuscular injection or 30 minutes following oral administration{01}

Adults—

Approximately 40 ng per mL after a single intramuscular 10-mg dose.{01}

Approximately 20 ng per mL after a single oral 10-mg dose.{01}

Approximately 70 to 100 ng per mL after multiple oral 60-mg doses (tablets or oral drops).{01}

Elimination:
    Renal—Following an oral dose of 40 mg, approximately 31% of the dose is excreted in the urine over a period of 4 days.{01}
    Feces—Following an oral dose of 40 mg, approximately 66% of the dose is excreted in the urine over a period of 4 days.{01}


Precautions to Consider

Carcinogenicity/Tumorigenicity

Studies conducted in rodents demonstrate that chronic administration of dopamine receptor blocking agents result in an increase in mammary neoplasms. However, neither clinical nor epidemiological studies conducted to date have shown an association between long-term administration of these medications and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time.{01}

Pregnancy/Reproduction

Pregnancy—
Studies have not been done in humans.{01}

Animal studies have not shown that domperidone has any teratogenic or primary embryotoxic effects on the fetus.{01}

Breast-feeding

Low concentrations of domperidone are found in the breastmilk. Therefore, nursing is not recommended by mothers receiving domperidone unless the expected benefits outweigh any potential risk. {01}

Pediatrics

The safety and efficacy in children have not been established.{01}


Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following drug classes, depending on the amount present, may also interact with this medication.

Anticholinergic drugs (seeAppendix II )    (concomitant administration of anticholinergic agents may minimize the effects of domperidone{01})


Azole antifungals    (the main metabolic pathway of domperidone is through CYP3A4; as inhibitors of CYP3A4, azole antifungals can block the metabolism of domperidone, resulting in increased plasma concentrations of domperidone; caution is indicated in the combined use of domperidone and azole antifungals{01})


Human immunodeficiency virus (HIV) protease inhibitors    (the main metabolic pathway of domperidone is through CYP3A4; as inhibitors of CYP3A4, HIV protease inhibitors can block the metabolism of domperidone, resulting in increased plasma concentrations of domperidone; caution is indicated in the combined use of domperidone and HIV protease inhibitors{01})


» Macrolide antibiotics    (the main metabolic pathway of domperidone is through CYP3A4; as inhibitors of CYP3A4, macrolide antibiotics can block the metabolism of domperidone, resulting in increased plasma concentrations of domperidone; caution is indicated in the combined use of domperidone and macrolide antibiotics{01})


» Monoamine oxidase (MAO) inhibitors    (use caution when using domperidone with MAO inhibitors{01})


Nefazodone    (the main metabolic pathway of domperidone is through CYP3A4; as an inhibitor of CYP3A4, nefazodone can block the metabolism of domperidone, resulting in increased plasma concentrations of domperidone; caution is indicated in the combined use of domperidone and nefazodone{01})


Sustained-release or enteric-coated formulations of drugs    (since domperidone enhances gastric and small intestinal motility, it may accelerate absorption of drugs from the small bowel while slowing absorption of drugs taken up from stomach, particularly those with sustained-release or enteric-coated formulations{01})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]), serum
Aspartate aminotransferase (AST [SGOT]), serum
Cholesterol, serum and
Prolactin, serum    (values may be increased{01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Gastrointestinal hemorrhage, mechanical obstruction or perforation    (stimulation of gastrointestinal motility may aggravate these conditions )


Hepatic impairment    (domperidone undergoes extensive first-pass metabolism. Drug accumulation may occur in patients with hepatic impairment{01})


» Sensitivity to domperidone{01}
» Prolactinoma    (domperidone may contribute to excessively high serum concentrations of prolactin in patients with a prolactin-releasing pituitary tumor{01})



Side/Adverse Effects

Note: Some of the side effects associated with domperidone are an extension of its dopamine antagonist properties. A majority of these side effects resolve spontaneously during continued therapy or are tolerated. However, more serious or troublesome side effects (e.g., galactorrhea, gynecomastia, or menstrual irregularities) can be dose-related and will respond to lowering the dose or discontinuing therapy.{01}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent
    
CNS effects{01} (dry mouth; headache)
    
conjunctivitis{01} (itching, redness, pain, or swelling of eye)
    
endocrinological effects{01} ( hot flushes; menstrual irregularities)
    
galactorrhea{01} (breast milk flowing from the nipple)
    
gynecomastia{01} (excessive development of the breast in the male)
    
mastalgia{01} (pain in the breast )
    
pruritus{01} ( itching)
    
rash{01}
    
stomatitis{01} (swelling of the mouth)
    
urticaria{01} (hives)

Incidence rare
    
Asthenia{01} (lack or loss of strength)
    
CNS effects{01} (dizziness; irritability; nervousness; thirst)
    
change in urinary frequency{01}
    
edema{01} (swelling of face, hands, lower legs, or feet )
    
extrapyramidal effects{01} (difficulty in speaking; loss of balance or muscle control)
    
gastrointestinal effects{01} (abdominal cramps; change in appetite; constipation; diarrhea; heartburn)
    
leg cramps{01}
    
lethargy{01} (drowsiness; mental dullness ; sluggishness; tiredness; weakness)
    
palpitations{01} (fast, irregular, pounding, or racing heartbeat or pulse)
    
dysuria{01} ( burning, difficult, or painful urination )
Note: Extrapyramidal side effects will usually reverse spontaneously as soon as treatment is stopped.{01}







Overdose
For more information on the management of overdose or unintentional ingestion, contact a poison control center (see Poison Control Center Listing).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
    
Arrhythmia{01} ( dizziness, fainting, fast, slow, or irregular heartbeat)
    
drowsiness{01}
    
disorientation{01} (confusion)
    
extrapyramidal reactions{01} (difficulty in speaking, loss of balance or muscle control)
    
hypotension{01} (dizziness, faintness, or light-headedness when getting up from a lying or sitting position )


Note: Symptoms are self-limiting and usually disappear within 24 hours.{01}


Treatment of overdose
There is no specific antidote or specific agent for domperidone overdose. However, anticholinergic agents , antiparkinsonian medications, or antihistamines with anticholinergic properties may be useful in controlling the extrapyramidal reactions associated with domperidone toxicity.{01}


To enhance elimination :
Gastric lavage as well as the administration of activated charcoal may be useful in facilitating the elimination of domperidone.{01}



Supportive care:
Close observation and supportive therapy are recommended.{01}

Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Domperidone (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to domperidone

Pregnancy—No human data is available. Not recommended for use during pregnancy unless the benefit outweighs the potential hazard.





Breast-feeding—Distributed into breast milk.




Use in children— Safety and efficacy of domperidone not established in children

Other medications, especially azole antifungals, human immunodeficiency virus (HIV) protease inhibitors, macrolide antibiotics, monoamine oxidase (MAO) inhibitors, nefazodone, or sustained-release or enteric-coated formulations of drugs

Proper use of this medication

» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next scheduled dose; not doubling doses

Precautions while using this medication
Obtaining medical attention if fainting, dizziness, irregular heartbeat or pulse, or other unusual symptoms occur


Side/adverse effects
Asthenia, change in urinary frequency, CNS effects (dry mouth, headache, nervousness, dizziness, thirst, irritability), conjunctivitis, dysuria, edema, endocrinological effects (hot flushes, menstrual irregularities, mastalgia, galactorrhea, and gynecomastia, extrapyramidal effects (difficulty in speaking and loss of balance or muscle control), gastrointestinal effects (abdominal cramps, diarrhea, heartburn, constipation, and changes in appetite), leg cramps, lethargy, palpitations, pruritus, stomatitis, and urticaria


General Dosing Information
For upper gastrointestinal motility disorders, the usual dose for adults is 10 mg 3 to 4 times a day administered orally 15 to 30 minutes before meals and at bedtime if required. However, in severe or resistant cases, the dose can be increased to a maximum of 20 mg 3 to 4 times a day.{01}

For nausea and vomiting associated with dopamine agonist antiparkinsonian agents, the usual dose for adults is 20 mg 3 to 4 times a day administered orally. However, higher doses may be required to achieve symptom control while titration of the antiparkinsonian medication is occurring.{01}


Oral Dosage Forms

Note: The dosing and strength of the dosage form available are expressed in terms of domperidone base (not the maleate salt).{01}


DOMPERIDONE MALEATE TABLETS

Usual Adult Dose
Upper gastrointestinal motility disorders
Oral, 1 tablet (10 mg base) 3 to 4 times a day 15 to 30 minutes before meals and at bedtime, if required.{01}

Nausea and vomiting associated with dopamine agonist antiparkinsonian agents
Oral, 2 tablets (20 mg base) 3 to 4 times a day {01}


Usual adult prescribing limits
Up to 20 mg 3 to 4 times a day.{01}

Usual Pediatric Dose
Dosage has not been established. {01}

Usual Geriatric Dose
See Usual adult dose.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


10 mg (base) (Rx) [Motilium ( microcrystalline cellulose)]

Packaging and storage:
Store between 15 and 30 °C (59 and 89 °F), in a tight container. Protect from light and moisture.{01}



Developed: 10/09/2000



References
  1. Product Information: Motilium(R), domperidone maleate. Janssen-Ortho, Toronto, Ontario, Canada (PI revised 1999) reviewed 7/2000.
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