Rabeprazole

Rabeprazole belongs to the Gastrointestinal Agent acts as a Proton Pump Inhibitor.

Rabeprazole is a proton pump inhibitor used to help gastrointestinal ulcers heal, to treat symptoms of gastroesophageal reflux disease (GERD), to eradicate Helicobacter pylori, and to treat hypersecretory conditions such as Zollinger-Ellison Syndrome.

Rabeprazole well absorbed from the gastrointestinal tract. Rabeprazole is 96.3% bound to human plasma proteins. Mainly metabolised via non-enzymatic reduction and to a lesser extent via CYP3A and CYP2C19 isoenzymes. Following a single 20 mg oral dose of ¹⁴C-labeled rabeprazole, approximately 90% of the drug was eliminated in the urine, primarily as thioether carboxylic acid; its glucuronide, and mercapturic acid metabolites. The remainder of the dose was recovered in the feces. Total recovery of radioactivity was 99.8%. No unchanged rabeprazole was recovered in the urine or feces.

Rabeprazole shows side effects like Headache, Nausea, vomiting, constipation, diarrhea, gas, sore throat.

Rabeprazole is available in the form of Oral Tablet and Oral Capsule.

Rabeprazole is available in India, US, Spain, Germany, Malaysia, Canada, US, Australia, China, and Italy.

Rabeprazole belongs to the Gastrointestinal Agent acts as a Proton Pump Inhibitor.

Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H2-receptor antagonist properties, but suppress gastric acid secretion by inhibiting the gastric H⁺/K⁺ATPase (hydrogen-potassium adenosine triphosphatase) at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, rabeprazole has been characterized as a gastric proton-pump inhibitor. Rabeprazole blocks the final step of gastric acid secretion. In gastric parietal cells, rabeprazole is protonated, accumulates, and is transformed to an active sulfenamide. When studied in vitro, rabeprazole is chemically activated at pH 1.2 with a half-life of 78 seconds.

The time required for Rabeprazole to show its onset of action may vary depending on the dose form.

The Duration of action of Rabeprazole remains in your body for an average duration of 24 hours.

Rabeprazole is anti-ulcer medicine used to treat conditions where your stomach produces too much acid. It relieves stress ulcers and acidity due to the intake of painkillers. Rabeprazole is used along with antibiotics to prevent ulcers.

Rabeprazole is available in the form of Oral Tablet and Oral Capsule.

Rabeprazole Tablet and Capsule is taken orally, usually in divided dose.

Rabeprazole belongs to the Gastrointestinal Agent acts as a Proton Pump Inhibitor.

Rabeprazole is potent proton pump inhibitor; suppresses gastric acid secretion by inhibiting the parietal cell H+/K+ ATP pump.

Rabeprazole is approved for use in the following clinical indications

Adult indication

• Aspiration prophylaxis in patients undergoing anaesthesia
• Barrett esophagus
• Dyspepsia, functional
• Eosinophilic esophagitis
• Gastroesophageal reflux disease
• H. pylori eradication
• Hypersecretory conditions
• Nonsteroidal anti-inflammatory drugs–induced ulcers, primary prevention
• Peptic ulcer disease, treatment and secondary prevention

Paediatric indication

• GERD, symptomatic
• Helicobacter pylori eradication

Adult Dose

• Aspiration prophylaxis in patients undergoing anaesthesia

Oral: 20 mg given the night before surgery and 20 mg given the morning of surgery.

• Barrett esophagus

Oral: 20 mg once daily; may increase the dose to 20 to 40 mg twice daily if needed to eliminate gastroesophageal reflux disease (GERD) symptoms or heal reflux esophagitis. Long-term maintenance therapy is recommended.

• Dyspepsia, functional

Oral: 20 mg once daily for up to 8 weeks; can be continued for a longer duration in patients with symptom improvement. Some experts recommend attempting to discontinue every 6 to 12 months to minimize the long-term risk of therapy.

• Eosinophilic esophagitis

Oral: 20 mg twice daily for an 8-week trial.

• Gastroesophageal reflux disease

Oral: 20 mg once daily. Where available, may start with 10 mg once daily and increase to 20 mg once daily after 4 to 8 weeks, if necessary.

• H. pylori eradication

Oral: 20 or 40 mg twice daily as part of an appropriate combination regimen with antibiotics.

• Hypersecretory conditions

Oral: Initial: 60 mg once daily.

• Nonsteroidal anti-inflammatory drugs–induced ulcers, primary prevention

Oral: 20 mg once daily for the duration of high-risk NSAID use.

• Peptic ulcer disease, treatment and secondary prevention

Oral: 20 mg once daily for 12 to 24 weeks or as long as the NSAID is used (Feldman 2021b); where available, may consider 5 or 10 mg once daily.

Pediatric Dose

• GERD, symptomatic

Children ≤11 years: Oral: Sprinkle capsules:

<15 kg: 5 mg once daily, if inadequate response may increase to 10 mg once daily.

≥15 kg: 10 mg once daily; higher doses of 20 mg/day have also been described.

• Helicobacter pylori eradication

Children and Adolescents <16 years:

6 to <10 kg: Oral: 10 mg twice daily.

10 to <30 kg: Oral: 15 mg twice daily.

≥30 kg: Oral: 20 mg twice daily.

Rabeprazole is available in the form of Oral Tablet and Oral Capsule.

• Dosage Adjustment in Hepatic impairment Patient

Mild-to-moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): Avoid use; if treatment is necessary, monitor for adverse reactions.

Rabeprazole is contraindicated in patients with

• Rabeprazole is contraindicated in patients with known hypersensitivity to rabeprazole, substituted benzimidazoles, or to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria .
• PPIs, including rabeprazole, are contraindicated with rilpivirine-containing products.

• Presence of Gastric Malignancy

Symptomatic response to therapy with rabeprazole does not preclude the presence of gastric malignancy. Patients with healed GERD were treated for up to 40 months with rabeprazole and monitored with serial gastric biopsies. Patients without H. pylori infection (221 of 326 patients) had no clinically important pathologic changes in the gastric mucosa. Patients with H. pylori infection at baseline (105 of 326 patients) had mild or moderate inflammation in the gastric body or mild inflammation in the gastric antrum. Patients with mild grades of infection or inflammation in the gastric body tended to change to moderate, whereas those graded moderate at baseline tended to remain stable. Patients with mild grades of infection or inflammation in the gastric antrum tended to remain stable. At baseline, 8% of patients had atrophy of glands in the gastric body and 15% had atrophy in the gastric antrum. At endpoint, 15% of patients had atrophy of glands in the gastric body and 11% had atrophy in the gastric antrum. Approximately 4% of patients had intestinal metaplasia at some point during follow-up, but no consistent changes were seen.

• Concomitant Use with Warfarin

Steady state interactions of rabeprazole and warfarin have not been adequately evaluated in patients. There have been reports of increased INR and prothrombin time in patients receiving a proton pump inhibitor and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with a proton pump inhibitor and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.

• Acute Interstitial Nephritis

Acute interstitial nephritis has been observed in patients taking PPIs including rabeprazole. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue rabeprazole if acute interstitial nephritis develops.

• Cyanocobalamin (vitamin B-12) Deficiency

Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B-12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed.

• Clostridium difficile Associated Diarrhea

Published observational studies suggest that PPI therapy like rabeprazole may be associated with an increased risk of Clostridium difficile associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents. 

• Bone Fracture

Several published observational studies in adults suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines.

• Hypomagnesemia

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), healthcare professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically.

• Concomitant Use of rabeprazole with Methotrexate

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients.

It is not known if rabeprazole is excreted in human milk; however, rabeprazole is present in rat milk. Because many drugs are excreted in milk, caution should be exercised when Rabeprazole is administered to a nursing woman.

Pregnancy Category C

There are no adequate and well-controlled studies with rabeprazole in pregnant women. No evidence of teratogenicity was seen in animal reproduction studies with rabeprazole at 13 and 8 times the human exposure at the recommended dose for GERD, in rats and rabbits, respectively. Changes in bone morphology were observed in offspring of rats treated with oral doses of a different PPI through most of pregnancy and lactation. Because of these findings, rabeprazole should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Common

Abdominal pain, diarrhea, vomiting, Peripheral edema, Constipation, flatulence, nausea, xerostomia, Hepatic encephalopathy, hepatitis, increased liver enzymes, Infection, Dizziness, headache, pain, Arthralgia, myalgia, Pharyngitis.

• Rare

Acute generalized exanthematous pustulosis, bullous rash, cutaneous lupus erythematous, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, Hyperammonemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, increased thyroid stimulating hormone level, Clostridioides difficile associated diarrhea, colitis, Agranulocytosis, hemolytic anemia, leukopenia, pancytopenia, polyp (fundic gland), thrombocytopenia, Hepatotoxicity (idiosyncratic), jaundice, Anaphylaxis, angioedema, Drug reaction with eosinophilia and systemic symptoms, Coma, delirium, disorientation, vertigo, Bone fracture, rhabdomyolysis, systemic lupus erythematosus, Blurred vision, Interstitial nephritis (including acute interstitial nephritis), renal disease, Pneumonia (interstitial).

• Drugs Metabolized by CYP450

Rabeprazole is metabolized by the cytochrome P450 (CYP450) drug metabolizing enzyme system. Studies in healthy subjects have shown that rabeprazole does not have clinically significant interactions with other drugs metabolized by the CYP450 system, such as warfarin and theophylline given as single oral doses, diazepam as a single intravenous dose, and phenytoin given as a single intravenous dose (with supplemental oral dosing). Steady state interactions of rabeprazole and other drugs metabolized by this enzyme system have not been studied in patients.

• Warfarin

There have been reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including rabeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death.

• Cyclosporine

In vitro incubations employing human liver microsomes indicated that rabeprazole inhibited cyclosporine metabolism with an IC50 of 62 micromolar, a concentration that is over 50 times higher than the Cmax in healthy volunteers following 14 days of dosing with 20 mg of rabeprazole. This degree of inhibition is similar to that by omeprazole at equivalent concentrations.

• Compounds Dependent on Gastric pH for Absorption

Due to its effects on gastric acid secretion, rabeprazole can reduce the absorption of drugs where gastric pH is an important determinant of their bioavailability. Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ketoconazole, atazanavir, iron salts, erlotinib, and mycophenolate mofetil (MMF) can decrease, while the absorption of drugs such as digoxin can increase during treatment with rabeprazole. Concomitant use of atazanavir and PPIs is not recommended. Coadministration of atazanavir with PPIs is expected to substantially decrease atazanavir plasma concentrations and thereby reduce its therapeutic effect. Co-administration of PPIs in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving PPIs and MMF. Use rabeprazole with caution in transplant patients receiving MMF.

• Drugs Metabolized by CYP2C19

In a clinical study in Japan evaluating rabeprazole in adult patients categorized by CYP2C19 genotype (n=6 per genotype category), gastric acid suppression was higher in poor metabolizers as compared to extensive metabolizers. This could be due to higher rabeprazole plasma levels in poor metabolizers. Whether or not interactions of rabeprazole sodium with other drugs metabolized by CYP2C19 would be different between extensive metabolizers and poor metabolizers has not been studied.

• Combined Administration with Clarithromycin

Combined administration consisting of rabeprazole, amoxicillin, and clarithromycin resulted in increases in plasma concentrations of rabeprazole and 14-hydroxyclarithromycin. Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions due to drug interactions. Because of these drug interactions, clarithromycin is contraindicated for co-administration with certain drugs.

• Methotrexate

Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of methotrexate with PPIs have been conducted.

• Clopidogrel

Concomitant administration of rabeprazole and clopidogrel in healthy subjects had no clinically meaningful effect on exposure to the active metabolite of clopidogrel. No dose adjustment of clopidogrel is necessary when administered with an approved dose of rabeprazole.

The common side effects of Rabeprazole include the following

• Common side effects

Headache, Nausea, vomiting, constipation, diarrhea, gas, sore throat.

• Rare side effects

Blistering, peeling, or bleeding skin; sores on the lips, nose, mouth, or genitals; swollen glands; shortness of breath; fever; or flu-like symptoms, Rash hives; itching; swelling of the eyes, face, lips, mouth, throat, or tongue, difficulty breathing or swallowing; or hoarseness, irregular, fast, or pounding heartbeat muscle spasms; uncontrollable shaking of a part of the body, excessive tiredness, lightheadedness, dizziness, or seizures, severe diarrhea with watery stools, stomach pain, or fever that does not go away, new or worsening joint pain; rash on cheeks or arms that is sensitive to sunlight, increased or decreased urination, blood in urine, fatigue, nausea, loss of appetite, fever, rash, or joint pain.

• Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies with rabeprazole in pregnant women. No evidence of teratogenicity was seen in animal reproduction studies with rabeprazole at 13 and 8 times the human exposure at the recommended dose for GERD, in rats and rabbits, respectively. Changes in bone morphology were observed in offspring of rats treated with oral doses of a different PPI through most of pregnancy and lactation. Because of these findings, rabeprazole should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Nursing Mothers

It is not known if rabeprazole is excreted in human milk; however, rabeprazole is present in rat milk. Because many drugs are excreted in milk, caution should be exercised when rabeprazole is administered to a nursing woman.

• Pediatric Use

Use of rabeprazole in neonates is strongly discouraged at this time for the treatment of GERD, based on the risk of prolonged acid suppression and lack of demonstrated safety and effectiveness in neonates.

• Geriatric Use

Out of the total number of subjects in clinical studies of rabeprazole, 19% were 65 years and over, while 4% were 75 years and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

There has been no experience with large overdoses with rabeprazole. Seven reports of accidental overdosage with rabeprazole have been received. The maximum reported overdose was 80 mg. There were no clinical signs or symptoms associated with any reported overdose. Patients with Zollinger Ellison syndrome have been treated with up to 120 mg rabeprazole QD. No specific antidote for rabeprazole is known. Rabeprazole is extensively protein bound and is not readily dialyzable. In the event of overdosage, treatment should be symptomatic and supportive.

Pharmacodynamic

Rabeprazole prevents the production of acid in the stomach. It reduces symptoms and prevents injury to the esophagus or stomach in patients with gastroesophageal reflux disease (GERD) or ulcers. Rabeprazole is also useful in conditions that produce too much stomach acid such as Zollinger-Ellison syndrome. Rabeprazole may also be used with antibiotics to get rid of bacteria that are associated with some ulcers. Rabeprazole is a selective and irreversible proton pump inhibitor, suppresses gastric acid secretion by specific inhibition of the H⁺, K⁺ -ATPase, which is found at the secretory surface of parietal cells. In doing so, it inhibits the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen.

Pharmacokinetics

• Absorption

Rabeprazole well absorbed from the gastrointestinal tract.

• Distribution

Rabeprazole is 96.3% bound to human plasma proteins.

• Metabolism and Excretion

Mainly metabolized via non-enzymatic reduction and to a lesser extent via CYP3A and CYP2C19 isoenzymes.

Following a single 20 mg oral dose of ¹⁴C-labeled rabeprazole, approximately 90% of the drug was eliminated in the urine, primarily as thioether carboxylic acid; its glucuronide, and mercapturic acid metabolites. The remainder of the dose was recovered in the feces. Total recovery of radioactivity was 99.8%. No unchanged rabeprazole was recovered in the urine or feces.

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