Rabeprazole

Keep all appointments with your doctor and the laboratory. Your doctor may order certain laboratory tests before and during your treatment, especially if you have severe diarrhea..

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Mechanism of Action

Proton pump inhibitor (PPI); binds to H+/K+-exchanging ATPase (proton pump) in gastric parietal cells, blocking acid secretion

Absorption

Bioavailability: 52%

Onset: Within 1 hr

Duration: 24 hr

Peak plasma time: 2-5 hr (tablet); 1-6.5 hr (capsule)

Distribution

Protein bound: 95-98%

Metabolism

Metabolism: Liver; extensively by hepatic P450 enzyme CYP2C19; second pathway through CYP3A4; also by non-enzymatic reduction

Metabolites (presumed inactive): Rabeprazole thioether, sulfone metabolite, desmethyl metabolite, desmethyl thioether, thioether carboxylic acid

CYP2C19 substrate (minor)

Elimination

Half-life elimination: 1-2 hr, depending on dose

Dialyzable: No

Total body clearance: 4-8 mL/min/kg

Excretion: Urine (90%); feces (10%)

CYP2C19 is an enzyme in the blood that is responsible for breaking down rabeprazole and other drugs in the body. Some patients have less of this protein in their bodies, affecting how much of the drug gets eliminated. Levels of CYP2C19 can vary greatly between individuals, and those having less of this protein are known as "poor metabolizers." 

CYP2C19 testing is done to determine whether you are a poor metabolizer. If you are a poor metabolizer, the levels of rabeprazole in your blood can become too high. As a result you may be at an increased risk of having more side effects from rabeprazole. 

Your doctor may adjust your dose of rabeprazole if you are a poor metabolizer.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if rabeprazole is excreted in human breast milk or if it can harm your nursing baby. Since many drugs can pass into breastmilk, and because of the possibility for serious reactions to infants from rabeprazole, a decision should be made to stop nursing or the drug. The importance of the drug to the mother should be considered.

Store rabeprazole in a dry place at room temperature, 59°F to 86°F (15°C to 30°C).

Keep rabeprazole and all medicines out of the reach of children.

Rabeprazole can cause kidney problems, an intestinal infection, or lupus (an autoimmune disorder).

Call your doctor right away if you have new or worsening joint pain, a skin rash that gets worse in sunlight, severe stomach pain, watery or bloody diarrhea, blood in your urine, or little or no urination.

Taking rabeprazole may increase your risk of bone fracture in the hip, wrist, or spine, especially if you take the medicine long term or more than once per day.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Bloating or swelling of the face, arms, hands, lower legs, or feet
• cough or hoarseness
• dark urine
• dry mouth
• fever or chills
• general tiredness and weakness
• light-colored stools
• lower back or side pain
• nausea and vomiting
• painful or difficult urination
• rapid weight gain
• tingling of the hands or feet
• unusual weight gain or loss
• yellow eyes and skin

• Bloody urine
• continuing ulcers or sores in the mouth
• convulsions (seizures)
• difficulty with breathing
• sore throat
• unusual bleeding or bruising
• unusual tiredness or weakness

• Back, leg, or stomach pains
• bleeding gums
• blood in the urine or stools
• bloody, black, or tarry stools
• change in consciousness
• clay-colored stools
• cloudy urine
• confusion about identity, place, person, and time
• continuing nausea or vomiting
• difficulty with swallowing
• dizziness
• drowsiness
• fast heartbeat
• general body swelling
• general feeling of tiredness or weakness
• greatly decreased frequency of urination or amount of urine
• headache
• high fever
• hives, itching, or skin rash
• holding false beliefs that cannot be changed by fact
• increase in the frequency of seizures
• joint or muscle pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of appetite
• loss of consciousness
• mood or mental changes
• muscle cramps
• muscle pain or stiffness
• muscle spasms (tetany) or twitching
• no blood pressure
• no breathing
• no pulse
• nosebleeds
• pale skin
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• seeing, hearing, or feeling things that are not there
• skin blisters
• sores, ulcers, or white spots on the lips or in the mouth
• swollen glands
• tightness in the chest
• trembling
• unpleasant breath odor
• unusual excitement, nervousness, or restlessness
• vomiting of blood

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bad, unusual, or unpleasant (after) taste
• change in taste

• Body aches or pain
• congestion
• constipation
• diarrhea
• excess air or gas in the stomach or intestines
• feeling weak
• full feeling
• heartburn
• numbness, tingling, pain, or weakness in the hands or feet
• pain
• passing gas
• runny nose
• sleepiness
• swollen joints
• tender, swollen glands in the neck
• voice changes

• Blistering, peeling, or loosening of the skin
• red, irritated eyes
• red skin lesions, often with a purple center

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Healing of Erosive or Ulcerative GERD in Adults

Rabeprazole Sodium Delayed-Release Tablets are indicated for short-term (4 to 8 weeks) treatment in the healing and symptomatic relief of erosive or ulcerative gastroesophageal reflux disease (GERD). For those patients who have not healed after 8 weeks of treatment, an additional 8-week course of Rabeprazole Sodium Delayed-Release Tablets may be considered.

Maintenance of Healing of Erosive or Ulcerative GERD in Adults

Rabeprazole Sodium Delayed-Release Tablets are indicated for maintaining healing and reduction in relapse rates of heartburn symptoms in patients with erosive or ulcerative gastroesophageal reflux disease (GERD Maintenance). Controlled studies do not extend beyond 12 months.

Treatment of Symptomatic GERD in Adults

Rabeprazole Sodium Delayed-Release Tablets are indicated for the treatment of daytime and nighttime heartburn and other symptoms associated with GERD in adults for up to 4 weeks.

Healing of Duodenal Ulcers in Adults

Rabeprazole Sodium Delayed-Release Tablets are indicated for short-term (up to four weeks) treatment in the healing and symptomatic relief of duodenal ulcers. Most patients heal within four weeks.

Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence in Adults

Rabeprazole Sodium Delayed-Release Tablets, in combination with amoxicillin and clarithromycin as a three drug regimen, are indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or history within the past 5 years) to eradicate H. pylori. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.

In patients who fail therapy, susceptibility testing should be done. If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted [see Clinical Pharmacology (12.2) and the full prescribing information for clarithromycin].

Treatment of Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome in Adults

Rabeprazole Sodium Delayed-Release Tablets are indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

Treatment of Symptomatic GERD in Adolescent Patients 12 Years of Age and Older

Rabeprazole Sodium Delayed-Release Tablets are indicated for the treatment of symptomatic GERD in adolescents 12 years of age and above for up to 8 weeks.

Healing of Erosive or Ulcerative GERD in Adults

In a U.S., multicenter, randomized, double-blind, placebo-controlled study, 103 patients were treated for up to eight weeks with placebo, 10 mg, 20 mg or 40 mg Rabeprazole Sodium Delayed-Release Tablets once daily. For this and all studies of GERD healing, only patients with GERD symptoms and at least grade 2 esophagitis (modified Hetzel-Dent grading scale) were eligible for entry. Endoscopic healing was defined as grade 0 or 1. Each Rabeprazole dose was significantly superior to placebo in producing endoscopic healing after four and eight weeks of treatment. The percentage of patients demonstrating endoscopic healing was as follows:

In addition, there was a statistically significant difference in favor of the Rabeprazole Sodium Delayed-Release Tablets 10 mg, 20 mg, and 40 mg doses compared to placebo at Weeks 4 and 8 regarding complete resolution of GERD heartburn frequency (p≤0.026). All Rabeprazole Sodium Delayed-Release Tablets groups reported significantly greater rates of complete resolution of GERD daytime heartburn severity compared to placebo at Weeks 4 and 8 (p≤0.036). Mean reductions from baseline in daily antacid dose were statistically significant for all Rabeprazole Sodium Delayed-Release Tablets groups when compared to placebo at both Weeks 4 and 8 (p≤0.007).

In a North American multicenter, randomized, double-blind, active-controlled study of 336 patients, the percentage of patients healed at endoscopy after four and eight weeks of treatment was statisticially superior in the patients treated with Rabeprazole Sodium Delayed-Release Tablets compared to ranitidine:

A dose of 20 mg once daily of Rabeprazole Sodium Delayed-Release Tablets was significantly more effective than ranitidine 150 mg four times daily in the percentage of patients with complete resolution of heartburn at Weeks 4 and 8 (p<0.001). Rabeprazole Sodium Delayed-Release Tablets was also more effective in complete resolution of daytime heartburn (p≤0.025), and nighttime heartburn (p≤0.012) at both Weeks 4 and 8, with significant differences by the end of the first week of the study. The recommended dosage of Rabeprazole Sodium Delayed-Release Tablets is 20 mg once daily for 4 to 8 weeks.

Long-term Maintenance of Healing of Erosive or Ulcerative GERD in Adults

The long-term maintenance of healing in patients with erosive or ulcerative GERD previously healed with gastric antisecretory therapy was assessed in two U.S., multicenter, randomized, double-blind, placebo-controlled studies of identical design of 52 weeks duration. The two studies randomized 209 and 285 patients, respectively, to receive either 10 mg or 20 mg of Rabeprazole Sodium Delayed-Release Tablets once daily or placebo. As demonstrated in Tables 9 and 10 below, patients treated with Rabeprazole Sodium Delayed-Release Tablets were significantly superior to placebo in both studies with respect to the maintenance of healing of GERD and the proportions of patients remaining free of heartburn symptoms at 52 weeks. The recommended dosage of Rabeprazole Sodium Delayed-Release Tablets is 20 mg once daily.

Treatment of Symptomatic GERD in Adults

Two U.S., multicenter, double-blind, placebo controlled studies were conducted in 316 adult patients with daytime and nighttime heartburn. Patients reported 5 or more periods of moderate to very severe heartburn during the placebo treatment phase the week prior to randomization. Patients were confirmed by endoscopy to have no esophageal erosions.

The percentage of heartburn free daytime and/or nighttime periods was greater with Rabeprazole Sodium Delayed-Release Tablets 20 mg compared to placebo over the 4 weeks of study in Study RAB-USA-2 (47% vs. 23%) and Study RAB-USA-3 (52% vs. 28%). The mean decreases from baseline in average daytime and nighttime heartburn scores were significantly greater for Rabeprazole Sodium Delayed-Release Tablets 20 mg as compared to placebo at week 4. Graphical displays depicting the daily mean daytime and nighttime scores are provided in Figures 2 to 5.

In addition, the combined analysis of these two studies showed 20mg of Rabeprazole Sodium Delayed-Release Tablets significantly improved other GERD-associated symptoms (regurgitation, belching, and early satiety) by week 4 compared with placebo (all p values < 0.005).

A dose of 20 mg Rabeprazole Sodium Delayed-Release Tablets also significantly reduced daily antacid consumption versus placebo over 4 weeks (p<0.001).

The recommended dosage of Rabeprazole Sodium Delayed-Release Tablets is 20 mg once daily for 4 weeks.

Healing of Duodenal Ulcers in Adults

In a U.S., randomized, double-blind, multicenter study assessing the effectiveness of 20 mg and 40 mg of Rabeprazole Sodium Delayed-Release Tablets once daily versus placebo for healing endoscopically defined duodenal ulcers, 100 patients were treated for up to four weeks. Rabeprazole Sodium Delayed-Release Tablets were significantly superior to placebo in producing healing of duodenal ulcers. The percentages of patients with endoscopic healing are presented below:

At Weeks 2 and 4, significantly more patients in the Rabeprazole Sodium Delayed-Release Tablets 20 and 40 mg groups reported complete resolution of ulcer pain frequency (p≤0.018), daytime pain severity (p≤0.023), and nighttime pain severity (p≤0.035) compared with placebo patients. The only exception was the 40 mg group versus placebo at Week 2 for duodenal ulcer pain frequency (p=0.094). Significant differences in resolution of daytime and nighttime pain were noted in both Rabeprazole Sodium Delayed-Release Tablets groups relative to placebo by the end of the first week of the study. Significant reductions in daily antacid use were also noted in both Rabeprazole Sodium Delayed-Release Tablets groups compared to placebo at Weeks 2 and 4 (p<0.001).

An international randomized, double-blind, active-controlled trial was conducted in 205 patients comparing 20 mg Rabeprazole Sodium Delayed-Release Tablets once daily with 20 mg omeprazole once daily. The study was designed to provide at least 80% power to exclude a difference of at least 10% between Rabeprazole Sodium Delayed-Release Tablets and omeprazole, assuming four-week healing response rates of 93% for both groups. In patients with endoscopically defined duodenal ulcers treated for up to four weeks, Rabeprazole Sodium Delayed-Release Tablets were comparable to omeprazole in producing healing of duodenal ulcers. The percentages of patients with endoscopic healing at two and four weeks are presented below:

Rabeprazole Sodium Delayed-Release Tablets and omeprazole were comparable in providing complete resolution of symptoms. The recommended dosage of Rabeprazole Sodium Delayed-Release Tablets is 20 mg once daily for 4 weeks.

Helicobacter pylori Eradication in Patients with Peptic Ulcer Disease or Symptomatic Non-Ulcer Disease in Adults

The U.S. multicenter study was a double-blind, parallel-group comparison of Rabeprazole Sodium Delayed-Release Tablets, amoxicillin, and clarithromycin for 3, 7, or 10 days vs. omeprazole, amoxicillin and clarithromycin for 10 days. Therapy consisted of Rabeprazole 20 mg twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily (RAC) or omeprazole 20 mg twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily (OAC). Patients with H. pylori infection were stratified in a 1:1 ratio for those with peptic ulcer disease (active or a history of ulcer in the past five years) [PUD] and those who were symptomatic but without peptic ulcer disease [NPUD], as determined by upper gastrointestinal endoscopy. The overall H.pylori eradication rates, defined as negative 13C-UBT for H. pylori ≥ 6 weeks from the end of the treatment are shown in the following table. The eradication rates in the 7-day and 10-day RAC regimens were found to be similar to 10-day OAC regimen using either the Intent-to-Treat (ITT) or Per-Protocol (PP) populations. Eradication rates in the RAC 3-day regimen were inferior to the other regimens.

The recommended dosage of Rabeprazole Sodium Delayed-Release Tablets is 20 mg twice daily with amoxicillin and clarithromycin for 7 days.

Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome in Adults

Twelve patients with idiopathic gastric hypersecretion or Zollinger-Ellison syndrome have been treated successfully with Rabeprazole Sodium Delayed-Release Tablets at doses from 20 to 120 mg for up to 12 months. Rabeprazole Sodium Delayed- Release Tablets produced satisfactory inhibition of gastric acid secretion in all patients and complete resolution of signs and symptoms of acid-peptic disease where present. Rabeprazole Sodium Delayed-Release Tablets also prevented recurrence of gastric hypersecretion and manifestations of acid-peptic disease in all patients. The high doses of Rabeprazole Sodium Delayed-Release Tablets used to treat this small cohort of patients with gastric hypersecretion were well tolerated.

The recommended starting dosage of Rabeprazole Sodium Delayed-Release Tablets is 60 mg once daily.

• Pariprazole
• Rabeprazole Sodium

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Sprinkle, Oral, as sodium:

AcipHex Sprinkle: 5 mg [contains fd&c blue #2 aluminum lake]

AcipHex Sprinkle: 10 mg [contains fd&c yellow #6 (sunset yellow)]

Tablet Delayed Release, Oral, as sodium:

Aciphex: 20 mg

Generic: 20 mg

In mild-to-moderate hepatic impairment, AUC approximately doubled, total clearance decreased to less than half, and Cmax increased ~20% (not significant).

Hypersensitivity (eg, anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, urticaria) to rabeprazole, other substituted benzimidazoles, or any component of the formulation; concomitant use with rilpivirine-containing products

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, nausea, vomiting, diarrhea, constipation, flatulence, or pharyngitis. Have patient report immediately to prescriber signs of low magnesium (mood changes; muscle pain or weakness; muscle cramps or spasms; seizures; tremors; lack of appetite; severe nausea or vomiting; or an abnormal heartbeat), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of lupus (rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, angina or shortness of breath, or swelling in the arms or legs), severe dizziness, passing out, severe abdominal pain, bone pain, chills, excessive weight loss, severe loss of strength and energy, signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools), or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.