Pantop DSR (Pantoprazole 40 mg + Domperidone SR 30 mg)

Composition

Component	Class	Dose per capsule
Pantoprazole	Proton Pump Inhibitor (PPI)	40 mg
Domperidone SR	Dopamine D2 antagonist / Prokinetic (slow release)	30 mg

Mechanism of Action

Pantoprazole

Pantoprazole is a substituted benzimidazole that irreversibly inhibits the H+/K+-ATPase (proton pump) on the secretory surface of gastric parietal cells. It requires activation in the acidic environment of parietal cell canaliculi, which is why it must be taken 30 minutes before meals (when the proton pumps are actively secreting). A single dose suppresses acid secretion for up to 24 hours.

Metabolized by hepatic CYP2C19 and CYP3A4
Available as delayed-release tablets or oral suspension to protect against gastric acid degradation

(Goodman & Gilman's Pharmacological Basis of Therapeutics)

Domperidone SR (Slow Release)

Domperidone is a peripheral dopamine D2 receptor antagonist. It works by:

Blocking D2 receptors in the upper GI tract - enhancing gastroduodenal contractions and coordination, accelerating gastric emptying
Acting on the chemoreceptor trigger zone (CTZ) - which lies outside the blood-brain barrier - giving it strong antiemetic properties
It does not readily cross the blood-brain barrier, so extrapyramidal side effects are minimal compared to metoclopramide

The SR (slow release) formulation ensures sustained therapeutic levels over time, allowing once-daily dosing.

(Yamada's Textbook of Gastroenterology; Goodman & Gilman's)

Indications / Uses

Condition	Rationale
GERD / Acid reflux	Pantoprazole reduces acid + domperidone reduces reflux by improving LES tone & gastric emptying
Peptic ulcer disease	Acid suppression promotes healing of gastric/duodenal ulcers
Functional dyspepsia	Relieves bloating, nausea, fullness, upper abdominal discomfort
Gastroparesis	Domperidone accelerates gastric emptying (especially in diabetic gastroparesis)
Nausea and vomiting	Antiemetic effect via CTZ blockade by domperidone
Zollinger-Ellison syndrome	Pantoprazole controls pathological hypersecretion

Dosage

Adults: 1 capsule once daily, 30 minutes before breakfast
Do not crush or chew (SR formulation must remain intact)
Duration: as prescribed, typically 4-8 weeks for ulcers/GERD

Pharmacokinetics

Parameter	Pantoprazole	Domperidone
Absorption	Rapidly absorbed after enteric coating dissolves	Rapidly absorbed; peak in ~30 min
Protein binding	High	Moderate
Metabolism	Hepatic - CYP2C19, CYP3A4	Hepatic - CYP3A4 (N-dealkylation)
Half-life	~1-2 hours	~7 hours
Excretion	Primarily renal	~2/3 fecal, ~1/3 renal

Side Effects

Common:

Dry mouth
Headache
Diarrhea / constipation
Flatulence, abdominal pain
Dizziness
Nausea

Domperidone-specific:

Hyperprolactinemia - galactorrhea, breast engorgement, gynecomastia, amenorrhea, impotence (due to prolactin elevation via pituitary lactotrophs which lack a blood-brain barrier)
Cardiac arrhythmias / QT prolongation - risk of serious ventricular arrhythmias and even sudden cardiac death, especially in:
- Patients >60 years
- Doses above 30 mg/day
- Patients with CYP3A4 genetic polymorphisms affecting domperidone metabolism
- ECG (QTc) should be assessed before and during treatment

Pantoprazole-specific (long-term use):

Hypomagnesemia, hyponatremia
Vitamin B12 deficiency
Increased fracture risk
C. difficile-associated diarrhea
Rebound acid hypersecretion on discontinuation
Interstitial nephritis (rare)

Contraindications

Known hypersensitivity to pantoprazole, domperidone, or any excipient
Gastrointestinal bleeding, obstruction, or perforation
Prolactinoma
Conditions where cardiac conduction is prolonged (QT prolongation, congenital long QT)
Concurrent use of CYP3A4 inhibitors that prolong QT interval (e.g., ketoconazole, erythromycin)
Severe hepatic impairment

Drug Interactions

Drug	Interaction
Ketoconazole / antifungals	Inhibit CYP3A4 - increase domperidone levels and QT risk
Macrolide antibiotics (erythromycin, clarithromycin)	QT prolongation risk additive
Clopidogrel	Pantoprazole may reduce antiplatelet effect (CYP2C19 competition)
Methotrexate	PPI may increase methotrexate toxicity
Atazanavir / HIV drugs	PPI reduces absorption

Special Populations

Elderly (>60 years): Use domperidone with caution - higher risk of cardiac arrhythmia
Pregnancy: Avoid unless clearly necessary; domperidone not well studied
Hepatic impairment: Reduce dose; both drugs are hepatically metabolized
Renal impairment: Dose adjustment generally not required for pantoprazole

Important Notes

Domperidone is not FDA-approved in the US (available only through expanded access/IND application). It is widely used in India, the UK, Europe, and many other countries.
The SR formulation of domperidone in Pantop DSR provides more stable plasma levels than immediate release, reducing peak-related side effects.
Take the capsule whole, before breakfast.

Sources: Goodman & Gilman's Pharmacological Basis of Therapeutics; Yamada's Textbook of Gastroenterology, 7th ed.; Katzung's Basic and Clinical Pharmacology, 16th ed.

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