Domperidone

Domperidone is a Dopamine receptor Antagonist class of drug belonging to Gastrointestinal / Antiemetic agent.

Domperidone is a dopamine receptor antagonist used as a peristaltic stimulant and anti-emetic agent for dyspepsia, indigestion, epigastric pain, nausea, and vomiting.

Domperidone is rapidly absorbed, having bioavailability is approximately 15%. The time taken to reach peak plasma concentration is approximately 30-60 minutes. Domperidone enters breast milk in small amounts. The Plasma protein binding is 91-93%. Domperidone is Rapidly and extensively metabolized in the liver by CYP3A4 isoenzyme via N-dealkylation and by CYP3A4, CYP1A2, and CYP2E1 isoenzymes via hydroxylation. Undergoes extensive first-pass metabolism. Mainly excreted Via urine 31% (approximately 10% as unchanged drug) and 66%; (10% as unchanged drug in faeces).

Domperidone shows side effects like Swelling of face, lips, eyelids, tongue, hands and feet, Difficulty in breathing, Skin rash, Breast pain and tenderness, Dry mouth, Chest pain, Dizziness and fainting, Extreme tiredness.

Domperidone is available in the form of Oral tablet, Oral suspension, and Suppositories.

Domperidone is available in India, Canada, US, China, Spain, Australia, France, Italy, and Germany.

Domperidone belongs to the Gastrointestinal / Antiemetic agent acts as a Dopamine receptor Antagonist.

Domperidone acts as a gastrointestinal emptying (delayed) adjunct and 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. Antiemetic: The antiemetic properties of domperidone are related to its dopamine receptor blocking activity at both the chemoreceptor trigger zone and at the gastric level. It has strong affinities for the D2 and D3 dopamine receptors, which are found in the chemoreceptor trigger zone, located just outside the blood brain barrier, which - among others - regulates nausea and vomiting.

The Onset and Duration of action of Domperidone is not clinically established.

The Tmax of Domperidone is approximately 30 minutes.

Domperidone is available in the form of Oral tablet, Oral suspension, and Suppositories.

Domperidone tablet and suspension is taken orally, while suppositories taken via rectal route, usually 3 times daily.

Domperidone is an anti-emetic medicine that is used to treat nausea and vomiting caused by delayed gastric emptying (the time it takes for food to pass from the stomach to the small intestine). It increases intestinal movements and facilitates the excretion of the bowel. It is used alone or in combination with other medicines for relieving nausea, vomiting and indigestion. Domperidone works by blocking certain substances that trigger nausea or vomiting.

Domperidone is a Dopamine receptor Antagonist class of drug belonging to Gastrointestinal / Antiemetic agent.

Domperidone has peripheral dopamine receptor blocking properties and does not readily cross the blood-brain barrier. It increases esophageal peristalsis and increases lower esophageal sphincter pressure, increases gastric motility and peristalsis, and enhances gastroduodenal coordination, therefore, facilitating gastric emptying and decreasing small bowel transit time.

Domperidone is approved for use in the following clinical indications

• GI motility disorders
• Nausea/vomiting associated with dopamine-agonist anti-Parkinson agents

• GI motility disorders

Oral: 10 mg 3 times daily (maximum: 30 mg/day).

• Nausea/vomiting associated with dopamine-agonist anti-Parkinson agents

Oral: 10 mg 3 times daily (maximum: 30 mg/day).

Domperidone is available in various strengths as 10mg, 10ml and 30mg.

Domperidone is available in the form of Oral tablet, Oral suspension, and Suppositories.

Domperidone is contraindicated in patients with

• Hypersensitivity to domperidone or any component of the formulation; prolactin-releasing pituitary tumor (prolactinoma)
• Known existing prolongation of cardiac conduction intervals, particularly QT
• Significant electrolyte disturbances
• Underlying cardiac disease (eg, heart failure); moderate or severe hepatic impairment
• Patients with GI hemorrhage, mechanical obstruction, or perforation
• Concomitant use with potent CYP3A4 inhibitors such as azole antifungals (eg, ketoconazole), macrolides (eg, erythromycin), protease inhibitors, or nefazodone; concomitant use with QT-prolonging drugs.

• Altered cardiac conduction

Do not exceed 30 mg/day. Avoid use of domperidone for the following: concomitant use of drugs which prolong the QTc interval and with potent CYP3A4 inhibitors which may increase domperidone exposure, existing prolongation of cardiac conduction intervals (particularly QT), significant electrolyte disturbances or underlying cardiac diseases (eg, heart failure). QTc prolongation, life-threatening tachyarrhythmias (eg, torsade de pointes), and cardiac arrest have been reported after use; these adverse effects may be precipitated in patients with preexisting prolonged cardiac conduction or other underlying cardiac disease, hypokalemia, or receiving other QTc-prolonging agents. The American College of Gastroenterology guidelines recommend baseline and follow-up ECGs and avoiding use if corrected QT is >450 msec in male patients or >470 msec in female patients.

• Elevated prolactin levels

May increase prolactin levels (dose-dependent response); may be asymptomatic (clinical consequence of chronically elevated prolactin is unknown) or may present symptomatically as galactorrhea, gynecomastia, amenorrhea, or impotence (reversible upon decreasing dose or discontinuing drug). Use is contraindicated in patients with prolactinomas.

• Breast cancer

Use caution when administering to patients with a personal or family history of breast cancer; evidence regarding an association between chronic use of dopamine-receptor antagonists and breast cancer is limited and nonconclusive.

• Hepatic impairment

Undergoes extensive hepatic metabolism; use is contraindicated in patients with moderate to severe hepatic impairment; use with caution in mild impairment.

• Renal impairment

Use with caution in patients with severe renal impairment; dosage and/or frequency of administration may need adjusted with repeated use and/or long-term therapy. Monitor renal function regularly, particularly with long-term therapy.

Consumption of alcohol is not recommended during treatment with Domperidone due to the increased risk of serious side effects such as dizziness, drowsiness, difficulty concentrating, gastrointestinal bleeding, weakness, fatigue, etc.

Common Adverse effects

• Xerostomia, Headache , migraine, Edema, palpitations, Pruritus, skin rash, urticaria, Galactorrhea not associated with childbirth, gynecomastia, hot flash, increased serum cholesterol, increased serum prolactin, increased thirst, menstrual disease, Abdominal cramps, acid regurgitation, change in appetite, constipation, diarrhea, heartburn, nausea, stomatitis, Dysuria, mastalgia, urinary frequency, Increased serum alanine aminotransferase, increased serum aspartate aminotransferase, Asthenia, dizziness, extrapyramidal reaction, insomnia, irritability, lethargy, nervousness, Lower limp cramp, Conjunctivitis.

Rare Adverse effects

• Prolonged QT interval on ECG, severe ventricular arrhythmia, torsades de pointes, Amenorrhea, Impotence, Lupus-like syndrome.

• Anticholinergic Agents

May diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).

• Bromocriptine

Domperidone may diminish the therapeutic effect of Bromocriptine.

• CYP3A4 Inducers (Strong)

May decrease the serum concentration of Domperidone.

• CYP3A4 Inhibitors (Moderate)

May increase the serum concentration of Domperidone.

• CYP3A4 Inhibitors (Strong)

May increase the serum concentration of Domperidone.

• Fosfomycin

Gastrointestinal Agents (Prokinetic) may decrease the serum concentration of Fosfomycin.

• Fusidic Acid (Systemic)

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

• Haloperidol

May enhance the QTc-prolonging effect of Domperidone.

• Lefamulin

May enhance the QTc-prolonging effect of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated.

• Monoamine Oxidase Inhibitors

May enhance the adverse/toxic effect of Domperidone. Domperidone may diminish the therapeutic effect of Monoamine Oxidase Inhibitors. Monoamine Oxidase Inhibitors may diminish the therapeutic effect of Domperidone.

• Ondansetron

Domperidone may enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

• Opioid Agonists

May diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).

• Pentamidine (Systemic)

Domperidone may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

• Pimozide

May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk).

• Posaconazole

May increase the serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities.

• QT-prolonging Agents (Highest Risk)

May enhance the QTc-prolonging effect of Domperidone.

• QT-prolonging Agents (Moderate Risk)

May enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

• QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk)

Domperidone may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Domperidone.

• QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk)

Domperidone may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk). QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase the serum concentration of Domperidone.

• QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk)

May enhance the QTc-prolonging effect of Domperidone. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Domperidone.

• Sertindole

May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk).

• Sirolimus (Conventional)

Gastrointestinal Agents (Prokinetic) may increase the serum concentration of Sirolimus (Conventional).

• Triptorelin

Hyperprolactinemic Agents may diminish the therapeutic effect of Triptorelin.

The common side effect of Domperidone include the following

Common

• Swelling of face, lips, eyelids, tongue, hands and feet, Difficulty in breathing, Skin rash, Breast pain and tenderness, Dry mouth, Chest pain, Dizziness and fainting, Extreme tiredness.

Rare

• Irregular heartbeat, Disrupted menstrual cycle.

• Pregnancy

Domperidone is not recommended for use in pregnant women as sufficient data is not available regarding its safety.

• Nursing Mothers

Information is not available.

• Pediatric Use

Domperidone is not recommended for use in children less than 12 years of age and weighing less than 35 kg since the safety and efficacy data is not available.

• Geriatric Use

Domperidone should be used with caution in elderly people. The risk of adverse effects is significantly high and hence treatment should begin with the lowest possible dose.

Symptoms: Altered consciousness, agitation, convulsions, disorientation, extrapyramidal reactions, and somnolence.

Management: Supportive and symptomatic treatment. Perform gastric lavage and administer activated charcoal. Monitor ECG for the possibility of QT interval prolongation. May administer anticholinergics or anti-Parkinsonian agents to control extrapyramidal reactions.

Pharmacodynamic

Domperidone is a specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic.

Pharmacokinetics

• Absorption

Domperidone is rapidly absorbed, having bioavailability is approximately 15%. The time taken to reach peak plasma concentration is approximately 30-60 minutes.

• Distribution

Domperidone enters breast milk in small amounts. The Plasma protein binding is 91-93%.

• Metabolism and Excretion

Domperidone is Rapidly and extensively metabolized in the liver by CYP3A4 isoenzyme via N-dealkylation and by CYP3A4, CYP1A2, and CYP2E1 isoenzymes via hydroxylation. Undergoes extensive first-pass metabolism. Mainly excreted Via urine 31% approximately 1% as unchanged drug) and 66%; 10% as unchanged drug in faeces.

• https://www.uptodate.com/contents/domperidone-united-states-available-via-fda-investigational-drug-ind-protocol-only-drug-information?search=domperidone&source=panel_search_result&selectedTitle=1~46&usage_type=panel&kp_tab=drug_general&display_rank=1
• https://www.drugs.com/domperidone.html
• https://go.drugbank.com/drugs/DB01184
• https://www.mims.com/philippines/drug/info/domperidone?mtype=generic
• https://www.practo.com/medicine-info/domperidone-10-mg-tablet-20102#:~:text=Domperidone 10 MG Tablet is,the emptying of the bowel.