What is Domperidone and How Does it Treat Gastroparesis?
Domperidone is a dopamine-2 receptor antagonist that is used to treat symptoms of gastroparesis, such as nausea, vomiting, bloating, and early satiety. It works by increasing the contractions of the stomach and small intestine, thereby accelerating gastric emptying. A key feature of domperidone is that, unlike metoclopramide, it does not readily cross the blood-brain barrier. This means it has a lower risk of causing central nervous system (CNS) side effects, such as extrapyramidal symptoms, which are more common with metoclopramide. It acts peripherally on the chemoreceptor trigger zone and the gut to produce its antiemetic and prokinetic effects.
For patients with gastroparesis who have not responded to other treatments or have experienced side effects from metoclopramide, domperidone is often considered a valuable alternative. In the United States, domperidone is not commercially available and must be accessed through a special FDA program via an Investigational New Drug (IND) application.
Proper Administration and Timing for Optimal Absorption
To achieve the maximum therapeutic benefit, it is critical to take domperidone correctly, following your doctor’s specific instructions. The timing of administration relative to meals is a key factor for ensuring proper absorption and effectiveness.
General Administration Guidelines
- Adults: The administration of domperidone should always follow the specific instructions provided by your healthcare professional.
- Long-Term Therapy: While typically used for short-term treatment of nausea, gastroparesis is a chronic condition, and long-term therapy may be required under appropriate medical supervision.
Timing Relative to Meals
Domperidone is best absorbed when taken on an empty stomach. Taking it after a meal can delay its absorption and reduce its effectiveness.
- Pre-Meal Administration: Take your dose 15 to 30 minutes before a meal or snack. This timing allows the medication to reach therapeutic levels and begin its prokinetic action by the time food enters the stomach.
- Before Bed: If necessary, a dose may be taken before sleep to manage nocturnal symptoms.
How to Administer the Medication
- Tablets: Swallow tablets whole with a glass of water. Do not crush or chew them.
- Liquid Suspension: If using the oral suspension, use the provided measuring syringe to ensure an accurate dose. A kitchen teaspoon should not be used.
What to Do If You Miss a Dose
If you forget to take a dose, take it as soon as you remember. However, if it is almost time for your next dose (e.g., less than 2 hours before), skip the missed dose and continue with your regular schedule. Never take a double dose to make up for a missed one.
Potential Side Effects and Safety Monitoring
Despite its favorable CNS side effect profile compared to metoclopramide, domperidone is not without risks, particularly concerning cardiac and endocrine systems. Due to these risks, careful monitoring by a healthcare professional is mandatory.
Key Safety Warnings
- Cardiac Risks: Domperidone has been associated with serious cardiac adverse events, including QT interval prolongation, cardiac arrhythmias (irregular heartbeat), cardiac arrest, and sudden death. This risk is higher with higher doses, in patients over 60, and in those with pre-existing heart conditions.
- Pre-Treatment ECG: Before starting domperidone, a baseline electrocardiogram (ECG) is recommended to check for pre-existing QT prolongation. Treatment is typically withheld if the corrected QT interval is already prolonged.
- Ongoing Monitoring: Ongoing cardiac activity monitoring, including regular ECGs, is advised, especially for long-term use.
- Endocrine Effects: Because it increases prolactin levels, domperidone can cause hyperprolactinemia. This can lead to side effects such as breast enlargement (gynecomastia) or lactation (galactorrhea), breast pain, and menstrual irregularities in women.
Common Side Effects
- Headache
- Dry mouth
- Diarrhea
- Anxiety or agitation
- Drowsiness
When to Seek Immediate Medical Help
Contact your doctor or seek emergency medical care immediately if you experience:
- A very fast or unusual heartbeat
- Signs of an allergic reaction, such as swelling of the face, lips, or throat
- Dizziness or fainting
- Sudden shortness of breath or chest pain
- Unusual or uncontrolled body movements
Important Drug Interactions and Contraindications
Domperidone should not be used in individuals with certain pre-existing conditions or those taking specific medications.
Contraindications
- Pre-existing heart conditions: Heart failure, prolonged QT interval, or severe electrolyte abnormalities (potassium, magnesium).
- Liver disease: Moderate to severe hepatic impairment.
- Gastrointestinal issues: Bleeding, blockage, or tear in the intestines.
- Pituitary gland tumor: Known as prolactinoma, due to domperidone's effect on prolactin.
Significant Drug Interactions
Domperidone is metabolized by the enzyme CYP3A4, so taking it with drugs that inhibit this enzyme can increase domperidone levels and heighten the risk of cardiac toxicity. Concomitant use with the following is generally contraindicated:
- Strong CYP3A4 inhibitors: Azole antifungals (e.g., ketoconazole, itraconazole), macrolide antibiotics (e.g., erythromycin, clarithromycin), HIV protease inhibitors (e.g., ritonavir), and specific antidepressants or antiarrhythmics.
- Other QT-prolonging medications: Including certain antibiotics (e.g., levofloxacin), antiarrhythmics (e.g., amiodarone), and some antipsychotics.
Comparison: Domperidone vs. Metoclopramide for Gastroparesis
| Feature | Domperidone | Metoclopramide |
|---|---|---|
| Mechanism | Dopamine D2 antagonist with peripheral action | Dopamine D2 antagonist with both peripheral and central action |
| CNS Side Effects | Minimally crosses blood-brain barrier, resulting in fewer CNS side effects | Crosses blood-brain barrier, higher risk of CNS side effects like tardive dyskinesia |
| Availability in US | Requires FDA Investigational New Drug (IND) protocol | FDA-approved, but with a black-box warning for tardive dyskinesia |
| Cardiac Risk | Small, increased risk of cardiac arrhythmias, especially with high doses or in susceptible individuals | Also has cardiac side effect potential, along with other centrally acting agents |
| Primary Use in GP | Second-line treatment, often for those refractory to or intolerant of metoclopramide | First-line treatment for diabetic and other forms of gastroparesis |
Conclusion
Domperidone can be a highly effective treatment for the challenging symptoms of gastroparesis, particularly for patients who have not found relief with other prokinetic agents like metoclopramide. To ensure safety and maximize efficacy, it is crucial to adhere to the correct administration protocol: taking the medication 15-30 minutes before meals and following the prescribed dosage. Given the medication's known cardiac risks, careful medical supervision, including baseline and regular ECG monitoring, is essential. Patients must be vigilant for any signs of adverse effects and communicate openly with their healthcare provider, especially regarding new symptoms, medications, or health changes. For more information on the FDA's guidance regarding domperidone, review their Information about Domperidone page.
