Rabeprazole (Aciphex) is a proton-pump inhibitor that irreversibly inhibits gastric acid secretion. It is used to treat patients with GERD, Gastric and Duodenal Ulcers, dyspepsia, hypersecretory states, and eradication of H.Pylori.

Rabeprazole Uses:

• Duodenal ulcers (tablets only):

  • It is indicated for short-term (4 weeks or fewer) treatment in the healing and symptomatic relief of duodenal ulcers in adults.

• Gastroesophageal reflux disease:

  • It is used to treat erosive or ulcerative (tablets only): Short-term (4 - 8 weeks) treatment in the healing and symptomatic relief of erosive or ulcerative gastroesophageal reflux disease (GERD) in adults; for maintaining healing and reduction in relapse rates of heartburn symptoms in adults with erosive or ulcerative GERD.
  • Symptomatic (non-erosive): Treatment of symptomatic GERD for up to 4 weeks in adults (tablets only), up to 8 weeks in children ≥12 years and adolescents (tablets only), and up to 12 weeks in children 1 to 11 years of age (capsules only).

• Helicobacter pylori eradication (tablets only):

  • It is used in combination with amoxicillin and clarithromycin as the triple regime for  H. pylori eradication and healing of duodenal ulcer disease (active or history of within the past 5 years)

• Pathological hypersecretory conditions (tablets only):

  • It is used for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome in adults.

• Off Label Use of Rabeprazole in Adults:

  • Dyspepsia;
  • Gastric ulcer (treatment);
  • NSAID-induced ulcer prophylaxis;
  • Prevention of recurrent gastric or duodenal ulcer bleeding postendoscopy;
  • Stress ulcer prophylaxis in critically-ill patients

Rabeprazole Dose in Adults

Rabeprazole Dose in the treatment of Duodenal ulcer: Tablets:

• Oral: 20 mg once  a day for ≤ 4 weeks

Rabeprazole Dose in the treatment of Dyspepsia (off-label):

• Oral: 20 mg once a day for up to 8 weeks

Rabeprazole Dose in the treatment of Gastric ulcer (off-label):

• Oral: 20 mg once a day for 8 weeks based on healing and/or ulcer complications

Rabeprazole Dose in the treatment of Gastroesophageal reflux disease (GERD): Tablets: Oral:

• Erosive or ulcerative GERD:

  • Treatment: 20 mg once a day for 4 - 8 weeks; If there is no sufficient response, the dose can be repeated up to an additional 8 weeks; maintenance: 20 mg once a day

• Symptomatic GERD (non-erosive):

  • Treatment: 20 mg once a day for ≤4 weeks; If there is no sufficient response dose can be repeated for an additional 4 weeks.

Rabeprazole Dose in the treatment of Helicobacter pylori eradication: Tablets: Oral:

• Manufacturer labeling:

  • 20 mg twice a day along with amoxicillin 1,000 mg and clarithromycin 500 mg twice a day for 7 days

• American College of Gastroenterology guidelines:

  • Clarithromycin triple regimen:

    • 20 - 40 mg twice a day along with clarithromycin 500 mg twice a day and either amoxicillin 1 g twice a day or metronidazole 500 mg 3 times per day
    • Continue regimen for 14 days.

Note:

• Do not use clarithromycin triple therapy in patients with  higher risk macrolide resistance e.g. prior macrolide exposure, local clarithromycin resistance rates ≥15%, eradication rates with clarithromycin-based regimens ≤85%)

• Bismuth quadruple regimen:

  • 20 mg twice a day along with tetracycline 500 mg 4 times a day, metronidazole 250 mg 4 times a day or 500 mg 3 or 4 times a day, and either bismuth subcitrate 120 - 300 mg 4 times a day or bismuth subsalicylate 300 mg 4 times a day;
  • Continue regimen for 10 - 14 days.

• Concomitant regimen:

  • 20 mg twice a day along with amoxicillin 1 g twice a day, clarithromycin 500 mg twice a day, and either metronidazole or tinidazole 500 mg twice a day
  • Continue regimen for 10 - 14 days.

• Sequential regimen:

  • 20 mg twice a day plus amoxicillin 1 g twice a day for 5 - 7 days; then
  • Continue rabeprazole along with clarithromycin 500 mg twice a day, and either metronidazole or tinidazole 500 mg twice a day for 5 - 7 days.

• Hybrid regimen:

  • 20 mg twice a day plus amoxicillin 1 g twice a day for 7 days; then continue rabeprazole and amoxicillin along with clarithromycin 500 mg twice a day, and either metronidazole or tinidazole 500 mg twice a day for 7 days.

• Levofloxacin triple regimen:

  • 20 mg twice a day along with amoxicillin 1 g twice a day and levofloxacin 500 mg once a day; continue regimen for 10 - 14 days

Rabeprazole Dose in the treatment of Hypersecretory conditions (including Zollinger-Ellison Syndrome): Tablets:

• Oral: Initial: 60 mg once a day and then further dose according to patient's needs (some may require divided doses). Doses as high as 100 mg once a day and 60 mg twice a day can be given, can be given as long as the clinical requirement.

Rabeprazole Dose in the treatment of NSAID-induced ulcer prophylaxis (off-label):

• Oral: 5 - 20 mg once a day for 12 - 24 weeks

Rabeprazole Dose in the Prevention of recurrent gastric or duodenal ulcer bleeding post endoscopy (off-label):

• Oral: 20 mg twice a day for 72 hours

• Discontinuation of therapy:

  • In order to avoid worsening or rebound symptoms, a step-down approach is considered in some cases.
  • Dose reduction by 50% is considered over 2 to 4 weeks.
  • Alternate drugs should be used if the patient is already on the lowest possible dose.
  • Patients should be reassessed in case of worsening symptoms or withdrawal.

Rabeprazole Dose in Childrens

Rabeprazole Dose in the treatment of symptomatic GERD:

Note: According to recommendation of guidelines, It can be used up to 4-8 weeks and then wean off with clinical response, if no response after 4 - 8 weeks, reevaluate diagnosis and consider referral to pediatric GI specialist

• Infants: Limited data available:

  • Oral: Sprinkle capsules: 5 - 10 mg once a day

• Children ≤11 years:

  • Oral: Sprinkle capsules:
    • <15 kg: 5 mg once a day; Dose can be increased up to 10 mg once a day.
    • ≥15 kg: 10 mg once a day, higher doses of 20 mg has been given

• Children ≥12 years and Adolescents:

  • Oral: Tablets: 20 mg once a day.

Rabeprazole Dose in the treatment of Helicobacter pylori eradication:

Note: Usually, it is used for 14 days for triple therapy along with 2 antimicrobials (eg, clarithromycin, metronidazole, amoxicillin); preferred agents determined by susceptibility. Bismuth may be added to regimens as an alternative if resistance is present or susceptibility is unknown.

• Children and Adolescents <16 years:

  • 6 to <10 kg: Oral: 10 mg twice a day.
  • 10 to <30 kg: Oral: 15 mg twice a day.
  • ≥30 kg: Oral: 20 mg twice a day.

• Discontinuation of therapy:

  • Based on experience in adults: In order to avoid worsening or rebound symptoms, a step-down approach is considered in some cases.
  • Dose reduction by 50% is considered over 2 to 4 weeks.
  • Alternate drugs should be used if the patient is already on the lowest possible dose.
  • Patients should be reassessed in case of worsening symptoms or withdrawal.

Pregnancy Risk Category: N (Not assigned)

• Recommendations for treating GERD in pregnancy are available.
• Lifestyle modification and other medications are the first treatment options for pregnant patients.
• Based on the available data, PPIs can be used when indicated by the physician.

Rabeprazole use during breastfeeding:

• It is unknown if Rabeprazole is excreted in breast milk.
• After considering the risks of infant exposure, benefits of breastfeeding to the baby, and benefits to the mother, Rabeprazole should not be administered.

Dose in Kidney Disease:

No dosage adjustment required

Dose in Liver disease:

• Mild-to-moderate impairment (Child-Pugh class A or B): No dosage adjustment required.
• Severe impairment (Child-Pugh class C): Avoid use; if treatment is required monitor for adverse reactions.

Common Side Effects of Rabeprazole:

• Gastrointestinal:

  • Diarrhea
  • Abdominal Pain
  • Vomiting

Less Common Side Effects of Rabeprazole:

• Cardiovascular:

  • Peripheral Edema

• Central Nervous System:

  • Headache
  • Pain
  • Dizziness

• Gastrointestinal:

  • Nausea
  • Flatulence
  • Constipation
  • Xerostomia

• Hepatic:

  • Hepatic Encephalopathy
  • Hepatitis
  • Increased Liver Enzymes

• Infection:

  • Infection

• Neuromuscular & Skeletal:

  • Arthralgia
  • Myalgia

• Respiratory:

  • Pharyngitis

Contraindications to Rabeprazole:

• Hypersensitivity to rabeprazole or other substitutedbenzimidazoles or any component of this formulation
• Concomitant use with rilpivirine-containing products

Warnings and precautions

• Atrophic gastritis

  • Atrophic gastritis may occur if omeprazole and rabeprazole are combined for long-term treatment

• Carcinoma

  • There are no reports of adenomatoid, dysplastic, or neoplastic changes of enterochromaffin-like (ECL) cells in the gastric mucosa have occurred.

• Clostridium difficile-associated diarrhea (formerly Clostridium), Clostridioides:

  • There has been an increase in the risk of CDAD due to the use of proton pump inhibitors, (PPIs).
  • CDAD should be considered for patients with diarrhea, especially elderly patients who are hospitalized.
  • The lowest effective dose of PPIs (including pantoprazole) should be administered and the duration should not exceed 30 minutes.

• Cutaneous and systemic Lupus Erythematosus

  • Rabeprazole has been linked to autoimmune diseases such as Lupus.
  • The majority of cases reported involved cutaneous lupus, which is most commonly subacute and can last for weeks or months.
  • It is rarer to get systemic lupus, which can occur in a matter of days. This is most common in young adults.
  • The patient must stop receiving treatment and be referred to the specialist.
  • After discontinuing treatment, symptoms usually improve in 4-12 weeks.

• Fractures

  • Increased bone fracture risk has been linked to PPIs such as rabeprazole.
  • The hip, spine and wrist are the most common fractures that PPIs cause.
  • Long-term therapy patients (more than one year) as well as those who take high doses PPIs must be evaluated for osteoporosis.
  • These patients require adequate calcium intake and vitamin D supplements.

• Polyps of the fundic gland:

  • Long-term (more than one) use of PPIs has been linked to an increase in risk of stomach polyps.
  • The best PPIs should not be taken for longer than necessary and at the lowest dose.
  • Diagnosis of gastrointestinal polyps can lead to dyspepsia or gastrointestinal bleeding, anemia or obstruction.
• Gastrointestinal infection (eg, Salmonella, Campylobacter):
  • These infections can be exacerbated by the use of proton pump inhibitors.

• Hypomagnesemia:

  • Long-term use of PPIs (three months or more) has been associated with hypomagnesemia, either symptomatic or asymptomatic.
  • Baseline serum magnesium levels should always be checked when PPIs are to be used for long-term purposes.
  • Patients taking concomitant medications which may cause hypomagnesemia, or medication that may increase the risk of arrhythmias, should have their baseline serum magnesium levels checked before initiating long-term PPIs.
  • When the medication is stopped along with magnesium supplementation, hypomagnesemia will usually disappear within 2 weeks.

• Interstitial nephritis:

  • Acute interstitial Nephritis may be a sign of idiopathic hypersensitivity reactions. This can occur at any stage during treatment.

• Vitamin B deficiency:

  • Long-term (more than two years) use may lead to malabsorption, which can manifest as diarrhea or deficiency in B complex vitamins.
  • Malabsorption is more common in younger patients and females.
  • When PPI treatment is stopped, the condition will improve.

• Gastric cancer:

  • PPIs can mask the symptoms of gastrointestinal malignancies.

• Hepatic impairment

  • It should be avoided in cases of severe hepatic impairment. If it is indicated, monitor carefully

Rabeprazole: Drug Interaction

Monitoring parameters:

• Magnesium levels before starting the therapy and then periodically if rabeprazole is being used for the long term or with concomitant use of digoxin, diuretics, or other drugs that cause hypomagnesemia
• Susceptibility testing recommended in patients who fail the H.pylori eradication regimen.

How to administer Rabeprazole?

• It can be taken with an anti-inflammatory.

Capsules

• It can be used 30 minutes before you prepare a meal.
• You can use the entire contents of an open capsule with any other food, or just the contents.
  • A small amount of soft foods (e.g., applesauce or fruit- or vegetable-based baby food, yogurt, etc.)
  • A small amount of liquid (eg infant formula, apple juice or pediatric electrolyte solutions)
  • Liquids and food should be kept at room temperature.
  • Do not keep the entire dose for more than 15 minutes after preparation.

Tablets

• Consume whole
• Do not crush, break, or chew.
• You can take it with or without food.
• Take after a meal if indicated for duodenal ulcers
• Take with your morning and evening meals if H. pylori is indicated.

Mechanism of action of Rabeprazole:

• The proton pump inhibitors block the (H+ and K+) ATPase enzyme, which is the last step in the production of gastric acid.
• This decreases the acid secretion within the gastric parietal cells.

The onset of action: Within 1 hour

Duration: 24 hours

Absorption: Oral: Well absorbed within 1 hour; food delayed absorption up to 4 hours or longer

Protein binding: 96.3%

Metabolism:

• Hepatic via CYP3A and 2C19 to inactive metabolites

Bioavailability: Tablet: ~52%

Half-life elimination (dose-dependent):

• Children ≤11 years: 2.5 hours
• Children ≥12 years and Adolescents: 20 mg tablet: 0.97 ± 0.19 hours
• Adults: 1 - 2 hours

Time to peak, plasma:

• Children ≤11 years: Sprinkle capsule: 2 - 4 hours
• Children ≥12 years and Adolescents: 20 mg tablet: 4.1 ± 0.45 hours
• Adults: Tablet: 2 - 5 hours; Sprinkle capsule: 1 - 6.5 hours

Excretion:

• Urine (90% primarily as thioether carboxylic acid metabolites)
• Remainder in feces

International Brand Names of Rabeprazole:

• Aciphex
• AcipHex Sprinkle
• Abbott-Rabeprazole
• APO-Rabeprazole
• DOM-Rabeprazole EC
• MYLAN-Rabeprazole
• Pariet
• PMS-Rabeprazole EC
• PRO-Rabeprazole
• RAN-Rabeprazole
• RIVA-Rabeprazole EC
• SANDOZ Rabeprazole
• TEVA-Rabeprazole EC
• Acifix
• Acilesol
• Aciprazol
• Ares
• Barole
• Bepra
• Gastrodine
• Gelbra
• Happi
• Hygigastin
• Noflux
• Pacredo
• Paliell
• Paramet
• Parbezol
• Paricel
• Pariet
• Parzol
• Promto
• Rabe
• Rabeact
• Rabeact-20
• Rabec
• Rabecid
• Rabegen
• Rabekind
• Rabeloc
• Rabeol
• Raberin
• Rabesta
• Rabestad
• Rabet
• Rabetra
• Rabezole
• Rabiet
• Rabister
• Rabium
• Rabtas
• Rapoxol
• Rapzol
• Rasonix
• Raxium
• Razit
• Razole
• Relitaz
• Renom
• Risol
• Veloz
• Zabep
• Zulbex

Rabeprazole Brand Names in Pakistan: