Paridon (Domperidone): A Motility Stimulant/Dopamine Antagonist

Paridon contains Domperidone, a dopamine antagonist that primarily acts as a gastroprokinetic agent and antiemetic. It is used to relieve various dyspeptic symptoms, treat nausea and vomiting, and aid in certain medical procedures. It belongs to the therapeutic class of Motility Stimulants / Dopamine antagonists / Prokinetic drugs.

How Paridon Works (Pharmacology)

Domperidone's actions are based on its dopamine receptor blocking effects:

• Chemoreceptor Trigger Zone (CTZ) Blockade: It principally blocks dopamine receptors in the CTZ, an area in the brain that triggers nausea and vomiting. This leads to its antiemetic (anti-vomiting) effect.
• Gastroprokinetic Action: By blocking dopamine receptors in the gastrointestinal tract, Domperidone enhances motility. It restores normal motility and tone of the upper GI tract, facilitates gastric emptying, enhances antral and duodenal peristalsis, and regulates pyloric contraction.
• Esophageal Effects: It also increases esophageal peristalsis and lower esophageal sphincter pressure, preventing gastric content regurgitation.
• Limited Blood-Brain Barrier Penetration: Due to its weak penetration across the blood-brain barrier, Domperidone has minimal effect on central dopaminergic receptors, thus generally avoiding psychotropic and neurological side effects often seen with other dopamine antagonists.

Key Indications & Benefits

Paridon is indicated for:

• Dyspeptic symptom complex, often associated with delayed gastric emptying, gastroesophageal reflux, and esophagitis, including:
  • Epigastric sense of fullness, abdominal distension, upper abdominal pain
  • Eructation, flatulence, early satiety
  • Nausea and vomiting
  • Heartburn with or without regurgitation of gastric contents
  • Non-ulcer dyspepsia
• Acute nausea and vomiting of functional, organic, infectious, dietetic origin, or induced by radiotherapy, drug therapy, or migraine.
• Parkinson's disease: Specifically for dopamine-agonist induced nausea and vomiting.
• Radiological studies: Speeding barium transit in follow-through radiological studies.

Dosage & Administration

Domperidone should be taken 15-30 minutes before meals and, if necessary, before retiring. The maximum period of treatment for acute nausea and vomiting is 12 weeks. Always consult a registered physician for medication use.

Oral Dosing (Tablet/Suspension/Paediatric Drops):

• Adults: 10-20 mg (1-2 tablets or 10-20 ml suspension), every 6-8 hours daily. Maximum dose is 80 mg daily.
• Children: 2-4 ml suspension/10 kg body weight OR 0.4-0.8 ml paediatric drops/10 kg body weight, every 6-8 hours daily.
• In dyspeptic symptom (specific guidance):
  • Adults: 10-20 mg (1-2 tablets or 10-20 ml suspension), every 6-8 hours daily.
  • Children: 0.2-0.4 mg/kg (2-4 ml suspension/10 kg or 0.4-0.8 ml paediatric drops/10 kg) body weight, every 6-8 hours daily.
• In acute and sub-acute conditions (mainly acute nausea and vomiting):
  • Adults: 20 mg (2 tablets or 20 ml suspension), every 6-8 hours daily.
  • Children: 0.2-0.4 mg/kg (2-4 ml suspension/10 kg or 0.4-0.8 ml paediatric drops/10 kg) body weight, every 6-8 hours daily. (Maximum treatment period for acute nausea/vomiting is 12 weeks).

Rectal Dosing (Suppositories):

• Adults (including elderly): 30-60 mg every 4-8 hours.
• Children: Maximum daily rectal dose is 30 mg for those weighing 10 to 25 kg. The dose may be divided throughout the day if necessary.
• Maximum treatment period is 12 weeks.

Important Considerations & Warnings

It is crucial to discuss your full medical history with your doctor before taking Paridon.

Contraindications:

• Known hypersensitivity to Domperidone or its components.
• Neonates.
• Whenever gastrointestinal stimulation might be dangerous (e.g., gastrointestinal hemorrhage, mechanical obstruction, or perforation).
• Patients with prolactin-releasing pituitary tumor (prolactinoma).

Side Effects:

• Rare: Transient intestinal cramps.
• Extrapyramidal phenomena: Rare in young children, exceptional in adults; reverse spontaneously upon stopping treatment.
• Hyperprolactinemia: Domperidone may increase plasma prolactin levels, which in rare cases can lead to neuroendocrinological phenomena such as galactorrhea (milk discharge) and gynecomastia (breast enlargement in males).
• Neurological side-effects: Cannot be totally excluded if the blood-brain barrier is immature (as in infants) or impaired.
• Rare allergic reactions: Rash and urticaria.

Pregnancy & Lactation:

• Pregnancy: Domperidone did not produce teratogenic effects in animals at high doses. However, like most medicines, it should only be used during the first trimester of pregnancy if justified by anticipated therapeutic benefit. No evidence of increased risk of malformations in humans.
• Lactation: Domperidone is excreted in breast milk (concentrations 4 times lower than plasma). It is not known if this is harmful to the newborn. Therefore, nursing is not recommended for mothers taking domperidone, unless expected benefits outweigh potential risks.

Precautions & Warnings:

• Children: Use with absolute caution in children, especially young children, due to an increased risk of extrapyramidal reactions because of an incompletely developed blood-brain barrier.
• Hepatic Impairment: Use with caution in patients with hepatic impairment, as domperidone is highly metabolized in the liver.
• Mental Alertness: Domperidone does not affect mental alertness.

Drug Interactions:

• Anticholinergic drugs: May antagonize the antidyspeptic effect of domperidone.
• Antacids and antisecretory drugs: Should not be given simultaneously with domperidone as they lower its oral bioavailability.
• CYP3A4 Inhibitors: Concomitant use of drugs that significantly inhibit CYP3A4 (the main metabolic pathway of domperidone) may result in increased plasma levels of domperidone. Examples include azole antifungals (e.g., ketoconazole), macrolide antibiotics (e.g., erythromycin), HIV protease inhibitors, nefazodone.
• Other orally administered drugs: Theoretically, due to gastro-kinetic effects, domperidone could influence the absorption of concomitantly administered drugs, especially sustained-release or enteric-coated formulations. However, it did not influence blood levels of digoxin or paracetamol in stabilized patients.
• Neuroleptics: Domperidone does not potentiate their action.
• Dopaminergic agonists (e.g., bromocriptine, L-dopa): Domperidone suppresses their unwanted peripheral effects (digestive disorders, nausea, vomiting) without counteracting their central properties.

Use in Special Populations

• Infants: Use with great caution and under close medical supervision during the first months of life due to incompletely developed metabolic and blood-brain barrier functions. The occurrence of neurological side effects cannot be totally excluded in infants under 1 year.
• Liver disorders: Use with caution in patients with hepatic impairment.
• Kidney disorders:
  • Severe renal insufficiency (serum creatinine >6 mg/100ml): Elimination half-life is increased, but plasma drug levels were lower than in healthy volunteers.
  • Single acute administration: Unlikely to need dose adjustment.
  • Repeated administration: Dosing frequency should be reduced to once or twice daily depending on severity, and dose may need reduction. Patients on prolonged therapy should be reviewed regularly.

Overdose Effects

• Symptoms of overdosage: Drowsiness, disorientation, and extrapyramidal reactions (especially in children).
• Management: In case of overdosage, administration of activated charcoal and close observation are recommended. Anticholinergic, antiparkinson drugs, or antihistamines with anticholinergic properties may be helpful in controlling extrapyramidal reactions.

Storage Conditions

Store below 30°C, Protected from light & moisture. Keep out of children's reach.