Usage
This combination medication is primarily prescribed for the prophylactic management of migraine, especially in cases accompanied by nausea, vomiting, pain, and fever. It is also used for the symptomatic treatment of migraine and other medical conditions where nausea, vomiting, fever and pain manifest concurrently. It’s pharmacological classifications include antiemetic, anti-migraine agent, calcium channel blocker, analgesic, and antipyretic.
Domperidone antagonizes dopamine and serotonin receptors in the chemoreceptor trigger zone (CTZ), preventing nausea and vomiting. It also has prokinetic effects, speeding up gastrointestinal motility. Flunarizine, a calcium channel blocker, prevents vasoconstriction in cerebral blood vessels, mitigating migraine headaches. Paracetamol inhibits prostaglandin synthesis, reducing pain and fever.
Alternate Names
While no specific alternate generic names exist, several brand names market this combination, including Migrest, Zerograin-Plus, Flurizone-DM, Domsi Plus and Migrasaf. Regional variations in names may also exist.
How It Works
Pharmacodynamics: Domperidone peripherally blocks dopamine D2 receptors and acts as a serotonin 5-HT4 receptor agonist and a 5-HT3 receptor antagonist. These actions suppress emesis, stimulate gastric motility, and reduce gastric emptying time. Flunarizine blocks calcium channels, preventing vasoconstriction and potentially inhibiting neuronal excitability. Paracetamol exerts analgesic and antipyretic effects by inhibiting prostaglandin synthesis in the central nervous system.
Pharmacokinetics: Domperidone is rapidly absorbed orally but has limited bioavailability due to first-pass metabolism. It is metabolized by CYP3A4 and eliminated via hepatic and renal routes. Flunarizine has high oral bioavailability, undergoes hepatic metabolism, and is excreted primarily in feces. Paracetamol is well-absorbed orally, undergoes hepatic metabolism (primarily glucuronidation and sulfation), and is eliminated by the kidneys.
Mode of Action: Domperidone inhibits dopamine receptors and serotonin receptors in the CTZ, suppressing vomiting reflex. It acts as a prokinetic agent by increasing upper gastrointestinal tract’s motility and decreasing stomach emptying time. Flunarizine blocks calcium influx into vascular smooth muscle, resulting in vasodilation and preventing migraine headache. Paracetamol inhibits COX enzymes in the central nervous system, reducing prostaglandin synthesis, thereby alleviating pain and fever.
Elimination Pathways: Domperidone is primarily excreted via the kidneys, Flunarizine via the kidneys and stool, and Paracetamol via the kidneys, after liver metabolism.
Dosage
Standard Dosage
Adults: A common dosage regimen is one tablet containing Domperidone 10mg, Flunarizine 5mg, and Paracetamol 500-650mg, taken up to three times daily. Dosing should be individualized based on patient response and tolerability.
Children: This combination is generally not recommended for children under 12 years of age. For older children, dosage must be carefully determined by a pediatrician considering age and weight.
Special Cases:
- Elderly Patients: Start with a lower dose due to increased sensitivity to side effects like drowsiness and cardiac issues.
- Patients with Renal Impairment: Dose adjustment may be needed to avoid accumulation of the drug.
- Patients with Hepatic Dysfunction: Contraindicated in severe hepatic impairment; use with caution in mild to moderate impairment and adjust dose as needed.
- Patients with Comorbid Conditions: Use with caution in patients with cardiac arrhythmias, congestive heart failure, prolonged QT interval, Parkinson’s disease, or a history of depression.
Clinical Use Cases
This specific combination is not typically used in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. In such cases, individual components might be used separately and according to specific guidelines.
Dosage Adjustments
Dosage adjustments are crucial based on patient-specific factors like renal/hepatic function, metabolic disorders, and potential drug interactions. Genetic polymorphisms affecting drug metabolism should also be considered.
Side Effects
Common Side Effects
Dry mouth, drowsiness, weight gain, increased appetite, fatigue, diarrhea, abdominal discomfort, indigestion, and menstrual irregularities.
Rare but Serious Side Effects
Extrapyramidal reactions, cardiac arrhythmias (including QT prolongation), liver damage, Stevens-Johnson syndrome, anaphylactic reactions, edema, jaundice, and erythema.
Long-Term Effects
Chronic complications from prolonged use may include extrapyramidal symptoms, weight gain, and potentially cardiac issues.
Adverse Drug Reactions (ADR)
Severe allergic reactions, cardiac events, and liver injury require immediate medical intervention.
Contraindications
Hypersensitivity to any component, severe hepatic impairment, gastrointestinal hemorrhage or obstruction, prolactin-releasing tumors, QT prolongation, ventricular arrhythmias, Parkinson’s disease, phenylketonuria, epilepsy, and breast cancer. Pregnancy and lactation are also generally considered contraindications.
Drug Interactions
CYP3A4 inhibitors (e.g., erythromycin, ketoconazole), calcium channel blockers (e.g., verapamil, diltiazem), CNS depressants (e.g., benzodiazepines), anti-arrhythmic drugs (e.g., amiodarone, quinidine), antibiotics (e.g., clarithromycin, moxifloxacin), metoclopramide, cisapride, warfarin, cholestyramine, carbamazepine, and estrogens. Alcohol should be avoided as it can exacerbate drowsiness.
Pregnancy and Breastfeeding
This combination is contraindicated in both pregnancy and breastfeeding. Domperidone is excreted in breast milk, and potential risks to the fetus have been reported.
Drug Profile Summary
- Mechanism of Action: Domperidone: Dopamine antagonist/serotonin modulator; Flunarizine: Calcium channel blocker; Paracetamol: Prostaglandin synthesis inhibitor.
- Side Effects: Drowsiness, dry mouth, weight gain, extrapyramidal symptoms, cardiac arrhythmias.
- Contraindications: Severe liver disease, pregnancy, breastfeeding, Parkinson’s disease, certain heart conditions.
- Drug Interactions: CYP3A4 inhibitors, calcium channel blockers, CNS depressants.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adult: One tablet (Domperidone 10mg, Flunarizine 5mg, Paracetamol 500-650mg) up to three times daily. Pediatric: Not recommended under 12 years; consult pediatrician for older children.
- Monitoring Parameters: Liver function tests, cardiac monitoring (ECG) for QT interval, especially in elderly and those on higher doses.
Popular Combinations
This combination itself is a common therapeutic strategy, but the individual components can be combined with other medications for specific conditions.
Precautions
Pre-existing medical conditions like liver or kidney disease should be assessed before prescribing. Caution is advised in elderly patients and those with renal impairment. Avoid alcohol. Driving or operating machinery should be restricted until the effects of the medication are known.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Domperidone + Flunarizine + Paracetamol?
A: The usual adult dose is one tablet containing 10mg Domperidone, 5mg Flunarizine, and 500-650mg Paracetamol, up to three times daily. Dosage should be adjusted for elderly patients and those with renal or hepatic impairment. Not generally recommended for children under 12.
Q2: Can this combination be used during pregnancy or breastfeeding?
A: No, it is contraindicated during pregnancy and breastfeeding due to potential fetal risks and excretion of domperidone in breast milk.
Q3: What are the most common side effects?
A: Common side effects include dry mouth, drowsiness, weight gain, increased appetite, fatigue, gastrointestinal disturbances, and menstrual irregularities.
Q4: Are there any serious side effects to watch out for?
A: Yes, rare but serious side effects include cardiac arrhythmias (especially QT prolongation), extrapyramidal reactions, liver damage, and allergic reactions. Seek immediate medical attention if these occur.
Q5: What should patients do if they miss a dose?
A: Take the missed dose as soon as remembered, unless it’s almost time for the next dose. Do not double the dose.
Q6: How does this combination interact with alcohol?
A: Alcohol should be avoided as it can exacerbate drowsiness and potentially increase the risk of other side effects.
Q7: Can this combination be used to treat an acute migraine attack?
A: It is primarily used for migraine prophylaxis, to prevent attacks. While it might help with some symptoms of an ongoing migraine, it might not be as effective as specific acute migraine treatments like triptans.
Q8: What precautions should be taken for elderly patients?
A: Elderly patients should generally start with a lower dose and be carefully monitored for side effects, especially drowsiness and cardiac issues.
Q9: What are the key drug interactions to consider?
A: Important drug interactions include those with CYP3A4 inhibitors, calcium channel blockers, CNS depressants, and certain cardiac medications. A detailed medication history is crucial.
Q10: What are the long-term implications of using this combination?
A: Long-term use may lead to weight gain, extrapyramidal symptoms, or potentially cardiac issues. Regular monitoring is important for early detection and management.
