[Posted 03/02/2011] ISSUE: FDA notified healthcare professionals and the public that prescription proton pump inhibitor (PPI) drugs may cause low serum magnesium levels (hypomagnesemia) if taken for prolonged periods of time (in most cases, longer than one year). Low serum magnesium levels can result in serious adverse events including muscle spasm (tetany), irregular heartbeat (arrhythmias), and convulsions (seizures); however, patients do not always have these symptoms. Treatment of hypomagnesemia generally requires magnesium supplements. In approximately one-quarter of the cases reviewed, magnesium supplementation alone did not improve low serum magnesium levels and the PPI had to be discontinued.
BACKGROUND: PPIs work by reducing the amount of acid in the stomach and are used to treat conditions such as gastroesophageal reflux disease (GERD), stomach and small intestine ulcers, and inflammation of the esophagus.
RECOMMENDATION: Healthcare professionals should consider obtaining serum magnesium levels prior to initiation of prescription PPI treatment in patients expected to be on these drugs for long periods of time, as well as patients who take PPIs with medications such as digoxin, diuretics or drugs that may cause hypomagnesemia. For patients taking digoxin, a heart medicine, this is especially important because low magnesium can increase the likelihood of serious side effects. Healthcare professionals should consider obtaining magnesium levels periodically in these patients. For additional information, refer to the Data Summary section of the FDA Drug Safety Communication. For more information visit the FDA website at: [Web] and [Web].
[Posted 05/25/2010] FDA notified healthcare professionals and patients of revisions to the prescription and over-the-counter [OTC] labels for proton pump inhibitors, which work by reducing the amount of acid in the stomach, to include new safety information about a possible increased risk of fractures of the hip, wrist, and spine with the use of these medications.
The new safety information is based on FDA's review of several epidemiological studies that found those at greatest risk for these fractures received high doses of proton pump inhibitors or used them for one year or more. The majority of the studies evaluated individuals 50 years of age or older and the increased risk of fracture primarily was observed in this age group. While the greatest increased risk for fractures in these studies involved people who had been taking prescription proton pump inhibitors for at least one year or who had been taking high doses of the prescription medications (not available over-the-counter), as a precaution, the “Drug Facts” label on the OTC proton pump inhibitors (indicated for 14 days of continuous use) also is being revised to include information about this risk. FDA recommends healthcare professionals, when prescribing proton pump inhibitors, should consider whether a lower dose or shorter duration of therapy would adequately treat the patient's condition.
The safety communication includes a data summary with a table and references which support the epidemiological studies reviewed for this communication. For more information visit the FDA website at: [Web] and [Web].
Some evidence for use of proton-pump inhibitors (e.g., omeprazole) for gastric acid suppressive therapy as an adjunct in the management of upper GI Crohn's disease,† including esophageal, gastroduodenal, and jejunoileal disease.
Administer orally; may give without regard to meals, but manufacturer recommends administration after morning meal in patients with duodenal ulcer.
When used in combination with clarithromycin and amoxicillin for treatment of H. pylori infection and duodenal ulcer disease, take all 3 drugs twice daily with morning and evening meals.
Swallow tablets intact; do not chew, crush, or split.
Antacids may be used concomitantly as needed for pain relief.
Dosage
Available as rabeprazole sodium; dosage expressed in terms of the salt.
Adults
GERD
GERD without Erosive Esophagitis
Oral
20 mg once daily for 4 weeks; may give additional 4 weeks if symptoms are not completely resolved.
Treatment of Erosive Esophagitis
Oral
20 mg once daily for 4–8 weeks. If not healed after 8 weeks, consider additional 8 weeks of therapy (up to 16 weeks for a single course).
Maintenance of Healing of Erosive Esophagitis
Oral
20 mg once daily. Chronic, lifelong therapy may be appropriate.
Duodenal Ulcer
Treatment of Active Duodenal Ulcer
Oral
20 mg once daily for up to 4 weeks; some patients may require additional therapy.
Helicobacter pylori Infection and Duodenal Ulcer Disease
Oral
Triple therapy: 20 mg twice daily for 7 days in conjunction with amoxicillin and clarithromycin.
Pathologic GI Hypersecretory Conditions (e.g., Zollinger-Ellison Syndrome)
Oral
60 mg once daily. Dosages up to 100 mg once daily or 60 mg twice daily have been used. Divided doses may be required. Adjust dosage as needed, continue treatment as long as necessary. Has been used continuously for up to 1 year.
Cautions
Contraindications
Known hypersensitivity to rabeprazole, any ingredient in the formulation, or other substituted benzimidazoles (e.g., esomeprazole, lansoprazole, pantoprazole, omeprazole).
Warnings/Precautions
General Precautions
GI Effects
Response to rabeprazole does not preclude presence of occult gastric neoplasm.
Respiratory Effects
Administration of proton-pump inhibitors has been associated with an increased risk for developing certain infections (e.g., community-acquired pneumonia).
Specific Populations
Pregnancy
Category B.
Lactation
Not known whether rabeprazole is distributed into milk; discontinue nursing or the drug.
Pediatric Use
Safety and efficacy not established in children <18 years of age.
Geriatric Use
No substantial differences in safety or efficacy relative to younger adults, but increased sensitivity cannot be ruled out.
Hepatic Impairment
Use with caution in patients with severe impairment.
Metabolized in the liver, principally by CYP3A and 2C19 isoenzymes.
Drugs Metabolized by Cytochrome P-450 Enzymes
No clinically important interactions with some drugs that are metabolized by CYP isoenzymes under single dose conditions; effects of rabeprazole have not been studied under steady-state conditions.
Absolute bioavailability with 20 mg dose is about 52%. Repeated dosing does not affect pharmacokinetics.
Onset
Within 1 hour. Median inhibition of 24-hour gastric acidity is 88% of maximum after first dose.
Food
High-fat meal may delay absorption but does not affect extent.
Special Populations
AUC increased 50–60% in Japanese males receiving a different rabeprazole formulation.
AUC doubled in patients with mild to moderate compensated cirrhosis. Peak plasma concentrations and AUCs increased 20% in patients with mild to moderate hepatic impairment.
In geriatric patients, peak plasma concentration increased by 60% and AUCs doubled.
Distribution
Extent
Not known whether rabeprazole crosses the placenta or is distributed into milk.
Prolonged binding to gastric parietal proton pump enzyme.
Plasma Protein Binding
Approximately 96%.
Elimination
Metabolism
Metabolized in the liver, principally by CYP3A and CYP2C19. Principal thioether and sulphone metabolites found in plasma are inactive.
Elimination Route
Excreted as metabolites in urine (90%); remainder in feces.
Half-life
1–2 hours.
Special Populations
In patients with mild to moderate compensated cirrhosis, elimination half-life was 2–3 times greater, and clearance decreased to less than one-half.
In patients with poor CYP2C19 metabolizer phenotype, metabolism is slower than in those with extensive (or rapid) metabolizer phenotype.
Stability
Storage
Oral
Tablets
25°C (may be exposed to 15–30°C).
Actions
Inhibits basal and stimulated gastric acid secretion.
Concentrates in acid conditions of parietal cell secretory canaliculi; forms active sulfenamide metabolite that binds to and inactivates hydrogen-potassium ATPase (proton- or acid-pump), blocking final step in secretion of hydrochloric acid. Sustained inactivation of hydrogen-potassium ATPase results in prolonged duration of action.
Suppresses gastric H. pylori in patients with duodenal ulcer and/or reflux esophagitis infected with the organism. Combined therapy with rabeprazole and one or more appropriate anti-infectives (e.g., amoxicillin, clarithromycin) can effectively eradicate H. pylori gastric infection.
Advice to Patients
Importance of swallowing tablets whole, without crushing or chewing.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs. Antacids may be used concomitantly as needed for pain relief.
Importance of women informing their clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
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