Usage
- This combination medication is primarily prescribed for the prophylaxis (prevention) of migraine headaches, especially in cases where nausea and vomiting are prominent symptoms. It may also be used to manage the acute symptoms of migraine attacks.
- Pharmacological Classification: Antiemetic (Domperidone), Calcium Channel Blocker (Flunarizine), Analgesic and Antipyretic (Paracetamol/Acetaminophen - commonly included in this combination).
Alternate Names
- No widely recognized alternate generic names exist for this specific combination. The individual components might be referred to by their international nonproprietary names (INN).
- Brand Names: The drug is marketed under various brand names like Migrest, Domsi Plus, and Zerograin-Plus. Availability might vary depending on the region.
How It Works
- Pharmacodynamics: Domperidone acts as a dopamine antagonist, primarily in the chemoreceptor trigger zone (CTZ) located in the brain, thus alleviating nausea and vomiting. It also increases gastrointestinal motility. Flunarizine, a calcium channel blocker, prevents the constriction of blood vessels in the brain, reducing the likelihood of migraine attacks. Paracetamol reduces pain and fever by acting on the central nervous system.
- Pharmacokinetics: Domperidone is rapidly absorbed orally, reaching peak plasma concentrations within an hour. It’s metabolized by the liver, primarily via CYP3A4 enzymes. Flunarizine is also well-absorbed orally and is highly lipophilic, leading to extensive distribution in tissues. Its metabolism is slow. Paracetamol is rapidly absorbed and metabolized in the liver. All three drugs are primarily eliminated through renal and hepatic pathways.
- Mode of Action: Domperidone blocks dopamine D2 receptors in the CTZ and peripherally, reducing nausea and vomiting. It also has prokinetic effects by blocking D2 receptors in the gastrointestinal tract. Flunarizine inhibits calcium influx into vascular smooth muscle, preventing vasoconstriction implicated in migraine pathogenesis. Paracetamol inhibits prostaglandin synthesis, reducing pain and fever.
Dosage
Standard Dosage
Adults:
- A typical dose might be one tablet containing Domperidone 10mg + Flunarizine 5mg + Paracetamol 325mg, taken two to three times a day. Dosage varies based on individual patient responses and clinical presentation.
Children:
- This combination is generally not recommended for children under 12 years of age. When used in children, careful dose adjustment based on weight and age is crucial.
Special Cases:
- Elderly Patients: Start with the lowest effective dose due to increased sensitivity to side effects.
- Patients with Renal Impairment: Dose adjustments may be necessary.
- Patients with Hepatic Dysfunction: Use with caution; dose adjustments are generally required.
- Patients with Comorbid Conditions: Consider potential interactions with other medications.
Clinical Use Cases
This combination is typically not used in the specific clinical settings of intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary role is in migraine prophylaxis and management of acute attacks.
Dosage Adjustments
- Dosage should be individualized based on patient response, renal/hepatic function, and concomitant medications.
Side Effects
Common Side Effects
- Drowsiness, Dry Mouth, Weight Gain, Constipation, Fatigue.
Rare but Serious Side Effects
- Extrapyramidal Symptoms (e.g., tremors, dystonia), Cardiac Arrhythmias, Hepatotoxicity.
Long-Term Effects
- Long-term use of flunarizine may be associated with extrapyramidal symptoms, especially in elderly patients.
Adverse Drug Reactions (ADR)
- Allergic Reactions, QT prolongation, Neuroleptic Malignant Syndrome (rare).
Contraindications
- Hypersensitivity to any of the components, Prolactin-releasing Pituitary Tumor, Severe Hepatic or Renal Impairment, Parkinson’s Disease, Concurrent use of QT-prolonging drugs, Pregnancy, Breastfeeding.
Drug Interactions
- CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin): Increased domperidone levels.
- QT Prolonging Drugs (e.g., certain antibiotics, antipsychotics): Increased risk of arrhythmia.
- CNS Depressants (e.g., alcohol, benzodiazepines): Enhanced sedation.
- Anticholinergic Drugs: May antagonize the prokinetic effects of domperidone.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Contraindicated. Domperidone is excreted in breast milk, and flunarizine has potential teratogenic effects.
Drug Profile Summary
- Mechanism of Action: Domperidone: Dopamine antagonist, Flunarizine: Calcium channel blocker, Paracetamol: Analgesic and antipyretic.
- Side Effects: Drowsiness, dry mouth, weight gain, extrapyramidal symptoms (rare).
- Contraindications: Hypersensitivity, hepatic/renal impairment, Parkinson’s disease, pregnancy.
- Drug Interactions: CYP3A4 inhibitors, QT prolonging drugs.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Varies; typically 10mg domperidone, 5mg flunarizine, 325mg paracetamol.
- Monitoring Parameters: Liver function tests, ECG (in long-term use).
Popular Combinations
While domperidone, flunarizine, and paracetamol are frequently combined, other combinations may be used depending on the patient’s specific needs.
Precautions
- Baseline ECG and liver function tests may be advisable, especially in long-term use. Monitor for extrapyramidal symptoms.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Domperidone + Flunarizine + Paracetamol?
A: The dosage varies depending on the specific formulation and the patient’s condition. A common dosage is one tablet containing 10mg domperidone, 5mg flunarizine, and 325mg paracetamol, taken two to three times a day.
Q2: Can this combination be used during pregnancy or breastfeeding?
A: No, it’s contraindicated in both pregnancy and breastfeeding.
Q3: What are the common side effects?
A: Drowsiness, dry mouth, weight gain, and constipation are common side effects.
Q4: Are there any serious side effects?
A: Rare but serious side effects include extrapyramidal symptoms, cardiac arrhythmias, and hepatotoxicity.
Q5: What are the drug interactions I should be aware of?
A: Interactions can occur with CYP3A4 inhibitors, QT-prolonging drugs, and CNS depressants.
Q6: How does this combination work for migraine?
A: Domperidone addresses nausea and vomiting, flunarizine prevents vasoconstriction, and paracetamol relieves pain and fever associated with migraine.
Q7: Can this combination be used in children?
A: It’s generally not recommended for children under 12. Careful dose adjustments are needed when used in children.
Q8: What precautions should I take when prescribing this medication?
A: Monitor for extrapyramidal symptoms, especially with long-term use. Baseline ECG and liver function tests may be advisable in certain cases.
Q9: Is it safe to operate machinery while taking this medication?
A: The combination may cause drowsiness, so caution is advised while driving or operating machinery.
