How safe is proton-pump inhibitor rabeprazole?
Dr. Muhammad Torequl Islam :
Rabeprazole (RPZ) is an inhibitor of the gastric proton pump (PPI). At present this medicine is quite common in Bangladesh. The use of this PPI seems to have increased significantly since after stopping use ranitidine. However, many studies have found that not only ranitidine but also omeprazole is one of the leading causes of cancer. Meanwhile, the efficacy of RPZ has been shown in many studies to be lower than that of ranitidine and omeprazole. RPZ works by inhibiting the gastric parietal cell proton pump (H+/K+-ATPase), thereby, reducing basal and peptone-stimulated acid secretion and provides the optimum anti-secretory effect. It is used to treat peptic ulcer disease, gastroesophageal reflux disease, and excess stomach acid production such as in Zollinger-Ellison syndrome, multiple endocrine adenomas, and systemic mastocytosis. It is also used in combination with other Helicobacter pylori medications. At present RPZ is widely used in gastro-esophageal reflux disease (GERD), gastric acid suppression, eradication of H. pylori, duodenal and gastric ulcers, and pathologic hypersecretory conditions. The US Food and Drug Administration (FDA) has approved RPZ for the treatment of above-mentioned conditions.
Common side effects of RPZ are – constipation, feeling weak, throat inflammation. However, it is evident to cause some serious side effects such as osteoporosis, low serum magnesium, Clostridium difficile infection, and pneumonia. Its use in pregnant and breastfeeding women is still remains unclear. It is evident to cause nausea, vomiting, diarrhea, headache, rhinitis, myalgia, pharyngitis, abdominal pain, dyspepsia, and eye disorders. It also increased abnormalities in serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels, low sodium levels, and changes in white blood cell (WBC) counts and gamma-glutamyl transferase (GGT) values than the ranitidine or omeprazole treatment.
All PPIs are evident to cause hypergastrinaemia and consequently change the GI cell histology. Patients receiving RPZ 20 mg therapy for 52 weeks significantly changed cell histology, 9% patients had diffuse hyperplasia and 4% had micronodular hyperplasia. Long-term uses of RPZ resulted incidence of atrophy of the gastric glands, increased serum gastrin levels, increased the pH of nocturnal acid breakthrough and nocturnal alkaline amplitude in gastric patients, caused interstitial pneumonia, low white blood cell count and pruritus in human. It increased the amoxicillin concentration in gastric juice by decreasing the gastric juice volume in rats. RPZ at 20?mg twice daily for 72 hours caused rebleeding within 3 days in 3.7% patients with a high-risk bleeding peptic ulcer. In a prospective study on 255 patients, it was seen that RPZ increased the incidence of diarrhea in patients receiving more than one month of this drug. It also exerted gastric anti-secretory effect on obese human, cytotoxic effects on human gastric cancers; reduced contraction frequencies, maximum contraction values, and muscle tone of human pylorus.
One study demonstrates that a woman (51 yr old) receiving RPZ for 5 years experienced with the witnessed seizure, tongue biting, muscle stiffness, and urinary incontinence with low potassium, calcium, magnesium, albumin, parathyroid hormone (PTH); high bicarbonate, creatinine, glucose, 1,25 dihydroxyvitamin D; and prolonged corrected QT (QTc) interval woman. In another study, RPZ (20 mg) and diclofenac sodium (100 sustained-release) along with (glucosamine + diacerine) and calcium plus vitamin D preparation on daily basis resulted black stools, mild epigastric tenderness, fatty liver grade-1, low hemoglobin (9.5 gm%), GI bleeding in a patient.
An oral administration of RPZ 20 mg caused hypochlorhydria in human, where a reduction of dasatinib maximum plasma concentration (Cmax) and area under the curve (AUC0-8) was seen by 92 and 78%, respectively. A case report suggests that RPZ 10 mg for a 6 months therapy developed collagenous colitis in human. So we should be careful in using RPZ, especially in its long-term use!
Rabeprazole (RPZ) is an inhibitor of the gastric proton pump (PPI). At present this medicine is quite common in Bangladesh. The use of this PPI seems to have increased significantly since after stopping use ranitidine. However, many studies have found that not only ranitidine but also omeprazole is one of the leading causes of cancer. Meanwhile, the efficacy of RPZ has been shown in many studies to be lower than that of ranitidine and omeprazole. RPZ works by inhibiting the gastric parietal cell proton pump (H+/K+-ATPase), thereby, reducing basal and peptone-stimulated acid secretion and provides the optimum anti-secretory effect. It is used to treat peptic ulcer disease, gastroesophageal reflux disease, and excess stomach acid production such as in Zollinger-Ellison syndrome, multiple endocrine adenomas, and systemic mastocytosis. It is also used in combination with other Helicobacter pylori medications. At present RPZ is widely used in gastro-esophageal reflux disease (GERD), gastric acid suppression, eradication of H. pylori, duodenal and gastric ulcers, and pathologic hypersecretory conditions. The US Food and Drug Administration (FDA) has approved RPZ for the treatment of above-mentioned conditions.
Common side effects of RPZ are – constipation, feeling weak, throat inflammation. However, it is evident to cause some serious side effects such as osteoporosis, low serum magnesium, Clostridium difficile infection, and pneumonia. Its use in pregnant and breastfeeding women is still remains unclear. It is evident to cause nausea, vomiting, diarrhea, headache, rhinitis, myalgia, pharyngitis, abdominal pain, dyspepsia, and eye disorders. It also increased abnormalities in serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels, low sodium levels, and changes in white blood cell (WBC) counts and gamma-glutamyl transferase (GGT) values than the ranitidine or omeprazole treatment.
All PPIs are evident to cause hypergastrinaemia and consequently change the GI cell histology. Patients receiving RPZ 20 mg therapy for 52 weeks significantly changed cell histology, 9% patients had diffuse hyperplasia and 4% had micronodular hyperplasia. Long-term uses of RPZ resulted incidence of atrophy of the gastric glands, increased serum gastrin levels, increased the pH of nocturnal acid breakthrough and nocturnal alkaline amplitude in gastric patients, caused interstitial pneumonia, low white blood cell count and pruritus in human. It increased the amoxicillin concentration in gastric juice by decreasing the gastric juice volume in rats. RPZ at 20?mg twice daily for 72 hours caused rebleeding within 3 days in 3.7% patients with a high-risk bleeding peptic ulcer. In a prospective study on 255 patients, it was seen that RPZ increased the incidence of diarrhea in patients receiving more than one month of this drug. It also exerted gastric anti-secretory effect on obese human, cytotoxic effects on human gastric cancers; reduced contraction frequencies, maximum contraction values, and muscle tone of human pylorus.
One study demonstrates that a woman (51 yr old) receiving RPZ for 5 years experienced with the witnessed seizure, tongue biting, muscle stiffness, and urinary incontinence with low potassium, calcium, magnesium, albumin, parathyroid hormone (PTH); high bicarbonate, creatinine, glucose, 1,25 dihydroxyvitamin D; and prolonged corrected QT (QTc) interval woman. In another study, RPZ (20 mg) and diclofenac sodium (100 sustained-release) along with (glucosamine + diacerine) and calcium plus vitamin D preparation on daily basis resulted black stools, mild epigastric tenderness, fatty liver grade-1, low hemoglobin (9.5 gm%), GI bleeding in a patient.
An oral administration of RPZ 20 mg caused hypochlorhydria in human, where a reduction of dasatinib maximum plasma concentration (Cmax) and area under the curve (AUC0-8) was seen by 92 and 78%, respectively. A case report suggests that RPZ 10 mg for a 6 months therapy developed collagenous colitis in human. So we should be careful in using RPZ, especially in its long-term use!
(Dr. Muhammad Torequl Islam is Assistant Professor, Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University. E-mail: [email protected])