Domperidone + Paracetamol

Usage

Domperidone + Paracetamol is prescribed for the symptomatic treatment of migraine attacks accompanied by nausea and vomiting. It also finds use in managing other medical conditions where nausea, vomiting, fever, and pain occur concurrently.

• Pharmacological Classification: This drug is a combination product belonging to the following classes:

  • Domperidone: Antiemetic, Prokinetic
  • Paracetamol: Analgesic, Antipyretic

• Mechanism of Action: Domperidone acts as a dopamine antagonist, primarily at the chemoreceptor trigger zone (CTZ) in the brain, reducing nausea and vomiting. It also increases gastrointestinal motility. Paracetamol inhibits prostaglandin synthesis, providing analgesic and antipyretic effects.

Alternate Names

This combination medication itself doesn’t have a specific international nonproprietary name (INN). It is recognized by the combination of its constituents’ names (Domperidone and Paracetamol).

• Brand Names: Domcet, Regamol (Paracetamol only)

How It Works

• Pharmacodynamics: Domperidone blocks dopamine receptors in the CTZ, decreasing nausea and vomiting. It also stimulates gastric emptying and increases lower esophageal sphincter tone. Paracetamol’s mechanism is not fully understood, but it’s believed to inhibit cyclooxygenase (COX) enzymes in the central nervous system, reducing prostaglandin synthesis and thereby decreasing pain and fever.
• Pharmacokinetics:
  • Domperidone: Orally administered Domperidone is rapidly absorbed, reaching peak plasma concentrations within 30-60 minutes. It undergoes hepatic metabolism via CYP3A4, and is primarily excreted through the bile and feces.
  • Paracetamol: Paracetamol is readily absorbed from the gastrointestinal tract, reaching peak plasma levels in about 30 minutes to 2 hours. It is primarily metabolized by the liver via glucuronidation and sulfation, with a small amount metabolized by CYP2E1 to a potentially hepatotoxic metabolite. It is excreted mainly in the urine.
• Receptor Binding/Enzyme Inhibition: Domperidone is a dopamine D2 receptor antagonist. Paracetamol is thought to inhibit COX enzymes, particularly in the CNS.
• Elimination Pathways: Domperidone is excreted mainly in the bile and feces, while Paracetamol is eliminated primarily in the urine, mostly as metabolites.

Dosage

Standard Dosage

Adults:

The typical adult dose is 10 mg domperidone and 500-1000 mg paracetamol, taken up to three times a day. Maximum 8 tablets of domperidone + paracetamol combination per day. Maximum 4g of paracetamol in 24 hours.

Children:

For children aged 5-12 years, the dosage of the combination will depend on the specific product. Paracetamol dosing is generally based on weight (e.g., 10-15 mg/kg every 4-6 hours). Domperidone is generally not recommended for children under 12. Consult a healthcare professional for precise pediatric dosing.

Special Cases:

• Elderly Patients: Use with caution; dose adjustment may be needed.
• Patients with Renal Impairment: Use with caution; dose adjustment may be necessary.
• Patients with Hepatic Dysfunction: Contraindicated in severe hepatic impairment. Use with caution in mild to moderate impairment; dosage adjustment may be necessary.
• Patients with Comorbid Conditions: Use with caution in patients with cardiac conditions.

Clinical Use Cases

The use of Domperidone + Paracetamol in these settings is not standard practice, and alternative medications might be more appropriate. Consult product specific literature for more information.

• Intubation
• Surgical Procedures
• Mechanical Ventilation
• Intensive Care Unit (ICU) Use
• Emergency Situations

Dosage Adjustments:

Dosage adjustments are necessary for patients with renal or hepatic impairment, elderly patients, and those with certain comorbid conditions. Follow healthcare professional’s recommendations.

Side Effects

Common Side Effects: Dry mouth, skin rash, anxiety, diarrhea, drowsiness, fatigue.

Rare but Serious Side Effects: Extrapyramidal reactions (dystonia, akathisia, parkinsonism), cardiac arrhythmias, QT prolongation, liver damage (with paracetamol overdose).

Long-Term Effects: May increase the risk of cardiac events with prolonged use, especially at higher doses or in the elderly.

Adverse Drug Reactions (ADR): Angioedema, anaphylaxis, Stevens-Johnson syndrome (rare).

Contraindications

• Hypersensitivity to domperidone or paracetamol.
• Gastrointestinal hemorrhage, obstruction, or perforation.
• Prolactin-releasing pituitary tumor (prolactinoma).
• Severe hepatic impairment.
• Concurrent use with drugs that prolong the QT interval (e.g. Amiodarone).

Drug Interactions

• CYP3A4 Inhibitors: Azole antifungals (ketoconazole, itraconazole), macrolide antibiotics (erythromycin, clarithromycin), HIV protease inhibitors (ritonavir), grapefruit juice can increase domperidone levels.
• Anticoagulants: Paracetamol may enhance the effect of warfarin.
• Metoclopramide: Concomitant use can increase the risk of extrapyramidal reactions.
• Anticholinergics: May antagonize the prokinetic effects of domperidone.
• Alcohol: May increase the risk of drowsiness and other side effects.

Pregnancy and Breastfeeding

• Pregnancy: Paracetamol is generally considered safe. Domperidone should be used with caution during pregnancy and only when the potential benefits outweigh the risks.
• Breastfeeding: Domperidone is excreted in breast milk. Exercise caution while breastfeeding. Paracetamol is considered safe to use while breastfeeding.

Drug Profile Summary

• Mechanism of Action: Domperidone: Dopamine antagonist, prokinetic. Paracetamol: Analgesic, antipyretic.
• Side Effects: Dry mouth, diarrhea, drowsiness, extrapyramidal reactions (rare), cardiac arrhythmias (rare).
• Contraindications: Hypersensitivity, GI obstruction/bleeding, prolactinoma, severe hepatic impairment.
• Drug Interactions: CYP3A4 inhibitors, anticoagulants, metoclopramide, alcohol.
• Pregnancy & Breastfeeding: Use with caution.
• Dosage: Adults: 10 mg domperidone + 500-1000 mg paracetamol, up to three times/day. Children: Consult a healthcare professional.
• Monitoring Parameters: Liver function tests (especially with long-term paracetamol use), ECG (for QT interval monitoring, especially with higher doses or in the elderly).

Popular Combinations

Domperidone + Paracetamol is sometimes combined with Tramadol for enhanced pain relief in moderate to severe pain.

Precautions

• Assess for allergies and pre-existing medical conditions, especially hepatic and renal impairment.
• Monitor for cardiac events, especially in elderly patients or those with underlying cardiac conditions.
• Avoid prolonged use of high doses of paracetamol due to hepatotoxicity risk.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Domperidone + Paracetamol?

A: The standard adult dose is 10 mg domperidone and 500-1000 mg paracetamol, taken up to three times a day. Pediatric and special population dosing should be determined by a healthcare professional.

Q2: What are the common side effects?

A: Common side effects include dry mouth, diarrhea, drowsiness, and skin rash.

Q3: Is it safe to use in pregnancy?

A: Paracetamol is generally considered safe during pregnancy. Domperidone should only be used if the potential benefits outweigh the risks. Consult an obstetrician for advice.

Q4: Can it be used while breastfeeding?

A: Both Domperidone and Paracetamol are excreted in breast milk. Use with caution while breastfeeding. Consult a pediatrician.

Q5: What are the contraindications?

A: Contraindications include hypersensitivity to either drug, gastrointestinal obstruction or bleeding, prolactinoma, and severe hepatic impairment.

Q6: Are there any significant drug interactions?

A: Yes, significant interactions can occur with CYP3A4 inhibitors, anticoagulants, metoclopramide, and alcohol.

Q7: What precautions should be taken when prescribing this medication?

A: Assess for pre-existing medical conditions, monitor liver function with long-term paracetamol use, and monitor for cardiac events, especially in at-risk populations.

Q8: Can this combination be used for postoperative nausea and vomiting?

A: It is not typically used as a first-line treatment for postoperative nausea and vomiting. Other antiemetics may be more appropriate.

Q9: Can this medication affect menstruation?

A: No, this medication doesn’t typically have a direct effect on menstruation.

Q10: What should be done in case of an overdose?

A: Seek immediate medical attention. Paracetamol overdose can cause severe liver damage.