Drug reference

Rabeprazole + Domperidone

Proton Pump Inhibitor · Anti-ulcerant, Anti-emetic

Also known as Razo-D, Rabekind-D, Rabicip-D, Aciloc-RD, Rablet-D, Veloz-D

Proton Pump InhibitorAnti-ulcerant, Anti-emeticATC A02BC04 (Rabeprazole); A03FA03 (Domperidone)

CDSCO approvedATC A02BC04 (Rabeprazole); A03FA03 (Domperidone)

Pharmacokineticsplasma · t hours

ONSET: 45min · Rabeprazole: 1 hour (acid suppression); Domperidone: 30-60 minutes (prokinetic effect).
PEAK: 3h · Rabeprazole: 2-4 hours; Domperidone: 0.5-1 hour.
t½: 1.5h · Rabeprazole: Approximately 1-2 hours; Domperidone: Approximately 7-9 hours (terminal half-life in healthy subjects).
DURATION: 10h · Rabeprazole: Acid suppression for >24 hours; Domperidone: Prokinetic effect for 8-12 hours (for SR formulation).

EXCRETION

—

not curated

INTERACTIONS

4 major

incl. contraindicated

PREGNANCY

Rabeprazole: Pregnancy Category B; Domperidone: Pregnancy Category C. The combination should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

FDA category + note

Top interactionssee all 12 →

AtazanavirContraindicatedTextbookG&G 14e · p1245-1266
LedipasvirSevereTextbookG&G 14e · p1238, p1242
RilpivirineSevereTextbookG&G 14e · p1245-1266
VelpatasvirSevereTextbookG&G 14e · p1239, p1242

Mechanism

Rabeprazole is a proton pump inhibitor that irreversibly blocks the H+/K+-ATPase enzyme system at the secretory surface of parietal cells, thereby suppressing gastric acid secretion. Domperidone is a peripheral D2 dopamine receptor antagonist that increases gastrointestinal motility and tone, facilitating gastric emptying and reducing esophageal sphincter pressure without affecting gastric acid secretion. The combination provides comprehensive relief by both reducing acid production and improving gut motility, addressing symptoms like reflux, heartburn, and bloating. Combination rationale: This fixed-dose combination provides a synergistic approach to managing acid-peptic disorders, particularly those complicated by impaired gastric motility. Rabeprazole effectively reduces gastric acid production, alleviating acid-related symptoms and promoting healing. Domperidone complements this by enhancing upper gastrointestinal motility, accelerating gastric emptying, and reducing reflux, thereby addressing symptoms like bloating, nausea, and regurgitation. This comprehensive action makes it beneficial for conditions like GERD and dyspepsia.

Indications

Gastroesophageal Reflux Disease (GERD)Non-ulcer dyspepsia with delayed gastric emptyingErosive esophagitisZollinger-Ellison syndrome and other pathological hypersecretory conditions

Dosing

Adult: Rabeprazole 20mg + Domperidone 10mg (immediate release) or Domperidone 30mg (sustained release), orally once daily, typically before breakfast for 4-8 weeks, or as directed by physician. Some formulations may offer Rabeprazole 40mg with Domperidone.
Pediatric: Generally not recommended for children below 12 years due to limited safety and efficacy data. For adolescents (12-18 years), use with caution and only if clearly indicated, under medical supervision.
Hepatic adjustment: Rabeprazole: No adjustment needed for mild to moderate hepatic impairment, but caution in severe impairment. Domperidone: Contraindicated in moderate to severe hepatic impairment. Use with caution in mild impairment.
Geriatric: Use with caution. Lower doses of domperidone may be considered due to increased risk of cardiac events in elderly. Renal and hepatic function should be assessed. Dosage adjustments may be necessary based on individual patient response and tolerability.
Max dose: Rabeprazole: 20mg/day (in this FDC). Domperidone: 30mg/day (for SR formulation) or 10mg three times daily (for IR formulation).

Pharmacokinetics

Onset

Rabeprazole: 1 hour (acid suppression); Domperidone: 30-60 minutes (prokinetic effect).

Peak effect

Rabeprazole: 2-4 hours; Domperidone: 0.5-1 hour.

Duration

Rabeprazole: Acid suppression for >24 hours; Domperidone: Prokinetic effect for 8-12 hours (for SR formulation).

Half-life

Rabeprazole: Approximately 1-2 hours; Domperidone: Approximately 7-9 hours (terminal half-life in healthy subjects).

Bioavailability

Rabeprazole: Approximately 52% (first dose); Domperidone: Oral bioavailability approximately 15% due to extensive first-pass metabolism.

Protein binding

Rabeprazole: Approximately 97%; Domperidone: 91-93%.

Metabolism

Rabeprazole: Hepatic, primarily via CYP2C19 and CYP3A4 enzymes; Domperidone: Hepatic, primarily via CYP3A4.

Excretion

Rabeprazole: Primarily renal (approximately 90%) with a small amount in feces; Domperidone: Approximately 66% in feces and 33% in urine.

Contraindications

Hypersensitivity to rabeprazole, domperidone, or any components
Patients with known prolongation of cardiac QTc intervals
Patients with significant electrolyte disturbances (hypokalemia, hypomagnesemia, hyperkalemia)
Patients with pre-existing cardiac disease, congestive heart failure, or history of Torsades de Pointes
Moderate to severe hepatic impairment (for domperidone component)
Patients with gastrointestinal hemorrhage, mechanical obstruction, or perforation
Patients with prolactin-releasing pituitary tumor (prolactinoma)
Concomitant use with potent CYP3A4 inhibitors (e.g., ketoconazole, erythromycin, clarithromycin) which can increase domperidone levels and QTc prolongation risk

Side effects

Common

HeadacheNauseaDiarrhea or constipationAbdominal painFlatulenceDry mouthDizzinessSkin rashWeakness or fatigue

Serious

QT interval prolongation, Torsades de Pointes, and other ventricular arrhythmias (especially with domperidone)
Severe hypersensitivity reactions (anaphylaxis, angioedema)
Clostridium difficile-associated diarrhea (CDAD) with PPIs
Acute interstitial nephritis (AIN) with PPIs
Bone fractures (long-term PPI use)
Subacute cutaneous lupus erythematosus (SCLE) with PPIs
Hypomagnesemia (long-term PPI use)
Extrapyramidal symptoms (dystonia, akathisia, parkinsonism, rare with standard doses of domperidone)
Hyperprolactinemia (leading to galactorrhea, gynecomastia, amenorrhea, decreased libido with domperidone)

Pregnancy & lactation

Pregnancy

Rabeprazole: Pregnancy Category B; Domperidone: Pregnancy Category C. The combination should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation

Both rabeprazole and domperidone are excreted in breast milk. Domperidone is known to increase prolactin levels and has been used off-label as a galactagogue; however, potential risks to the infant (especially cardiac effects) must be considered. Use during lactation is generally discouraged unless the potential benefit justifies the potential risk to the infant, with close monitoring.

Drug interactions

Atazanavir

Contraindicated

Textbook

Substantially reduced atazanavir concentrations, leading to loss of antiviral effectiveness.

Proton pump inhibitors should be avoided in patients receiving atazanavir without ritonavir.

Source: G&G 14e · p1245-1266

Ledipasvir

Severe

Textbook

Reduced ledipasvir concentrations, potentially leading to treatment failure/relapse.

If PPIs must be used, their doses should not exceed the equivalent of 20 mg omeprazole once daily. Omeprazole must be administered simultaneously with LDV/SOF in the fasted state.

Source: G&G 14e · p1238, p1242

Rilpivirine

Severe

Textbook

Reduced absorption and plasma concentrations of rilpivirine, potentially leading to loss of efficacy.

Should not be given with proton pump inhibitors.

Source: G&G 14e · p1245-1266

Velpatasvir

Severe

Textbook

Reduced velpatasvir concentrations, potentially leading to treatment failure.

PPI doses should not exceed the equivalent of 20 mg omeprazole daily. SOF/VEL should be taken with food 4 hours prior to a PPI dose. Velpatasvir requires acidic gastric pH.

Source: G&G 14e · p1239, p1242

Aceclofenac + Paracetamol

Moderate

Textbook

Increased risk of small intestine damage, despite reducing duodenal and gastric ulceration.

Consider the overall GI risk, including small intestine, when coadministering.

Source: G&G 14e · p834

Aceclofenac

Moderate

Textbook

Increased risk of small intestine damage, despite reducing duodenal and gastric ulceration.

Consider the overall GI risk, including small intestine, when coadministering.