Aciphex

Name: Aciphex

What is rabeprazole, and how does it work (mechanism of action)?

Rabeprazole is an oral drug that is used for the treatment of conditions caused by acid. It is in a class of drugs called proton pump inhibitors or PPIs which block the production of acid by the stomach. Other drugs in the same class include:

  • lansoprazole (Prevacid),
  • omeprazole (Prilosec),
  • pantoprazole (Protonix),
  • esomeprazole (Nexium), and
  • dexlansoprazole (Dexilant).

PPIs are used for the treatment of acid-caused conditions such as stomach and duodenal ulcers, gastroesophageal reflux disease (GERD) and Zollinger-Ellison Syndrome. Rabeprazole, like other PPIs, blocks the pump in the wall of the stomach that secretes acid into the stomach. By blocking the pump, the secretion of acid into the stomach is decreased, and this allows ulcers in the stomach and esophagus to heal. The FDA approved rabeprazole in August 1999.

What are the uses for rabeprazole?

Rabeprazole is used for treating ulcers of the stomach and duodenum, erosive or ulcerative gastroesophageal reflux disease (GERD) and Zollinger-Ellison Syndrome (in which there is overproduction of acid caused by tumors). It also is used with antibiotics for eradicating Helicobacter pylori infections of the stomach that, along with acid, are responsible for many ulcers.

Is rabeprazole safe to take if I'm pregnant or breastfeeding?

Use in pregnant women has not been adequately evaluated.

Rabeprazole has not been studied in nursing women.

What is the most important information I should know about rabeprazole?

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use. Rabeprazole is not for immediate relief of heartburn symptoms.

What should I avoid while taking rabeprazole?

This medicine can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

Interactions for AcipHex

Metabolized in the liver, principally by CYP3A and 2C19 isoenzymes.1 7 8 9

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.1

Drugs that Cause Hypomagnesemia

Potential pharmacologic interaction (possible increased risk of hypomagnesemia).327 Consider monitoring magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter.1 327 (See Hypomagnesemia under Cautions.)

Specific Drugs

Drug

Interaction

Comments

Amoxicillin

Increased rabeprazole and 14-hydroxyclarithromycin AUC and plasma concentrations when administered with amoxicillin and clarithromycin1

Not expected to result in toxicity1

Antacids

No clinically important effects on rabeprazole pharmacokinetics1

Atazanavir

Possible altered oral absorption of atazanavir, resulting in decreased plasma atazanavir concentrations; possible loss of virologic response1 42

Manufacturer of rabeprazole states that concomitant administration with atazanavir is not recommended1

Antiretroviral treatment-naive patients: If a proton-pump inhibitor is used concomitantly with atazanavir, administer ritonavir-boosted atazanavir (atazanavir 300 mg and ritonavir 100 mg once daily with food); administer the proton-pump inhibitor approximately 12 hours before ritonavir-boosted atazanavir41 42

For treatment-naive patients, dosage of proton-pump inhibitor should not exceed omeprazole 20 mg daily (or equivalent)41 42

Antiretroviral treatment-experienced patients: Concomitant use of proton-pump inhibitors with atazanavir not recommended41 42

Clarithromycin

Increased rabeprazole and 14-hydroxyclarithromycin AUC and plasma concentrations when administered with amoxicillin and clarithromycin1

Not expected to result in toxicity1

Clopidogrel

Certain CYP2C19 inhibitors (e.g., omeprazole, esomeprazole) reduce exposure to clopidogrel’s active metabolite and decrease platelet inhibitory effect;223 224 225 228 232 233 236 350 potentially may reduce clopidogrel’s clinical efficacy219 220 221 224 229 230 234 235 236 237 238 240 311

Dexlansoprazole, lansoprazole, or pantoprazole had less effect on clopidogrel's antiplatelet activity than did omeprazole or esomeprazole224 350 351

Assess risks and benefits of concomitant proton-pump inhibitor and clopidogrel use in individual patients237 240 243 248 250

American College of Cardiology Foundation/American College of Gastroenterology/American Heart Association (ACCF/ACG/AHA) states that GI bleeding risk reduction with concomitant proton-pump inhibitor in patients with risk factors for GI bleeding (e.g., advanced age; concomitant use of warfarin, corticosteroids, or NSAIAs; H. pylori infection) may outweigh potential reduction in cardiovascular efficacy of antiplatelet treatment associated with a drug-drug interaction.311 In patients without such risk factors, ACCF/ACG/AHA states that risk/benefit balance may favor use of antiplatelet therapy without a proton-pump inhibitor.311

If concomitant therapy with a proton-pump inhibitor and clopidogrel is deemed necessary, consider using an agent with little or no CYP2C19-inhibitory activity;47 48 49 224 230 350 alternatively, consider using a histamine H2-receptor antagonist (ranitidine, famotidine, nizatidine)47 48 230 but not cimetidine (also a potent CYP2C19 inhibitor)232 233

Cyclosporine

Rabeprazole inhibited cyclosporine metabolism in vitro1

Diazepam

No pharmacokinetic interaction observed after single doses1

Digoxin

Hypomagnesemia (e.g., resulting from long-term use of proton-pump inhibitors) sensitizes the myocardium to digoxin and, thus, may increase risk of digoxin-induced cardiotoxic effects327 331

See table entry for gastric pH-dependent drugs

Consider monitoring magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter1 327

Diuretics (i.e., loop or thiazide diuretics)

Possible increased risk of hypomagnesemia1 327

Consider monitoring magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter1 327

Fosamprenavir

Use of esomeprazole with fosamprenavir (with or without ritonavir) did not substantially affect concentrations of amprenavir (active metabolite of fosamprenavir)345

No dosage adjustment required when proton-pump inhibitors used with fosamprenavir (with or without ritonavir)41 345

Gastric pH-dependent drugs (e.g., digoxin, ketoconazole)

Rabeprazole may alter drug absorption1

Monitor if used concomitantly1

Lopinavir

Lopinavir/ritonavir: Omeprazole had no clinically important effect on plasma concentrations or AUC of lopinavir41 344

No dosage adjustment required when proton-pump inhibitors used with lopinavir/ritonavir41

Methotrexate (high-dose)

Possible delayed clearance and increased serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate; possible methotrexate toxicity1 334

Reported mainly with high-dose methotrexate (300 mg/m2 to 12 g/m2),1 but also reported with low dosages (e.g., 15 mg per week)

Manufacturer of rabeprazole recommends considering temporary discontinuance of proton-pump inhibitor therapy in some patients receiving high-dose methotrexate1

Some clinicians recommend withholding the proton-pump inhibitor for several days before and after administration of either high-dose or low-dose methotrexate or, alternatively, substituting a histamine H2-receptor antagonist for the proton-pump inhibitor334

Phenytoin

No pharmacokinetic interaction observed after single doses1

Raltegravir

Omeprazole increased peak plasma concentration and AUC of raltegravir41 348

No dosage adjustment recommended when proton-pump inhibitors used with raltegravir41 348

Rilpivirine

Omeprazole decreased plasma concentrations and AUC of rilpivirine41 343

Concomitant use of rilpivirine and proton-pump inhibitors contraindicated41 343

Saquinavir

Ritonavir-boosted saquinavir: Omeprazole increased peak plasma concentration and AUC of saquinavir41 346

Caution advised if proton-pump inhibitor used with ritonavir-boosted saquinavir; monitor for saquinavir toxicity41 346

Sucralfate

Possible delayed proton-pump inhibitor absorption and decreased bioavailability 34

Administer proton-pump inhibitor at least 30 minutes before sucralfate34

Theophylline

No pharmacokinetic interaction observed after single doses1

Warfarin

Potential for increased INR and PT1

Monitor PT and INR1

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

RABEprazole Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, delayed-release (enteric-coated)

20 mg

AcipHex

Eisai (also promoted by Janssen [formerly Ortho-McNeil-Janssen])

Before Using Aciphex

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Use of rabeprazole for treating gastroesophageal reflux disease (GERD) is not recommended in children younger than 1 year. Appropriate studies have not been performed on the relationship of age to the effects of rabeprazole for treating ulcers associated with infections, duodenal ulcers, or Zollinger-Ellison syndrome in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of rabeprazole in the elderly.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Rilpivirine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Atazanavir
  • Bosutinib
  • Cilostazol
  • Clopidogrel
  • Dasatinib
  • Digoxin
  • Erlotinib
  • Eslicarbazepine Acetate
  • Gefitinib
  • Ketoconazole
  • Ledipasvir
  • Methotrexate
  • Mycophenolate Mofetil
  • Nelfinavir
  • Nilotinib
  • Pazopanib
  • Saquinavir
  • Velpatasvir
  • Vismodegib

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Levothyroxine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

  • Cranberry

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Broken bones, history of or
  • Diarrhea, history of or
  • Hypomagnesemia (low magnesium levels), history of or
  • Osteoporosis (weak bones), history of or
  • Systemic lupus erythematosus (SLE) or
  • Vitamin B12 deficiency—Use with caution. May make these conditions worse.
  • Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Proper Use of rabeprazole

This section provides information on the proper use of a number of products that contain rabeprazole. It may not be specific to Aciphex. Please read with care.

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine comes with a Medication Guide. Read and follow the instructions carefully. Ask your doctor or pharmacist if you have any questions.

Swallow the delayed-release tablet whole. Do not crush, chew, or split the tablet. You may take this medicine with or without food. If your doctor tells you to take the medicine with food, follow those instructions.

For children using the delayed-release capsules:

  • Do not swallow the capsule whole.
  • Take the capsule 30 minutes before a meal.
  • Open the capsule and pour the contents on a small amount of soft food (eg, applesauce, fruit or vegetable baby food, yogurt) or in a small amount of liquid (eg, infant formula, apple juice, or pediatric electrolyte solution (Pedialyte®).
  • Take the mixture within 15 minutes. Swallow the mixture without chewing. Do not save it for later use.

If you are taking this medicine to treat an ulcer associated with an infection, take it together with the antibiotics (eg, amoxicillin, clarithromycin) at the same time of day.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (delayed-release tablets):
    • To treat duodenal ulcers:
      • Adults—20 milligrams (mg) once a day after the morning meal.
      • Children—Use and dose must be determined by your doctor.
    • To treat duodenal ulcers with H. pylori infection:
      • Adults—20 milligrams (mg) taken with a meal 2 times a day for 7 days. The dose is usually taken together with clarithromycin and amoxicillin.
      • Children—Use and dose must be determined by your doctor.
    • To treat gastroesophageal reflux disease (GERD):
      • Adults—20 milligrams (mg) once a day.
      • Children 12 years of age and older—20 mg once a day.
      • Children younger than 12 years—Use is not recommended.
    • To prevent gastroesophageal reflux disease (GERD):
      • Adults—20 milligrams (mg) once a day.
      • Children—Use and dose must be determined by your doctor.
    • To treat Zollinger-Ellison syndrome:
      • Adults—At first, 60 milligrams (mg) once a day. Your doctor may adjust your dose if needed.
      • Children—Use and dose must be determined by your doctor.
  • For oral dosage form (delayed-release capsules):
    • To treat gastroesophageal reflux disease (GERD):
      • Children 1 to 11 years and weighing 15 kilograms (kg) or more—10 milligrams (mg) once a day.
      • Children 1 to 11 years and weighing less than 15 kg—5 mg once a day. Your doctor may adjust your dose as needed.
      • Children younger than 1 year—Use is not recommended.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Dosage and administration

Table 1 shows the recommended dosage of Aciphex delayed-release tablets in adults and adolescent patients 12 years of age and older. The use of Aciphex delayed-release tablets is not recommended for use in pediatric patients 1 year to less than 12 years of age because the lowest available tablet strength (20 mg) exceeds the recommended dose for these patients. Use another rabeprazole formulation for pediatric patients 1 year to less than 12 years of age.

Table 1: Recommended Dosage and Duration of Aciphex Delayed-Release Tablets in Adults and Adolescents 12 Years of Age and Older
Indication Dosage of Aciphex delayed-release tablets Treatment Duration
Adults
Healing of Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD) 20 mg once daily 4 to 8 weeks*
Maintenance of Healing of Erosive or Ulcerative GERD 20 mg once daily Controlled studies do not extend beyond 12 months
Symptomatic GERD in Adults 20 mg once daily Up to 4 weeks**
Healing of Duodenal Ulcers 20 mg once daily after the morning meal Up to 4 weeks***
Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Aciphex 20 mg
Amoxicillin 1000 mg 
Clarithromycin 500 mg 
Take all three medications twice daily with morning and evening meals; it is important that patients comply with the full 7-day regimen [see Clinical Studies (14.5)]
7 days
Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome Starting dose 60 mg once daily then adjust to patient needs; some patients require divided doses
Dosages of 100 mg once daily and 60 mg twice daily have been administered
As long as clinically indicated
Some patients with Zollinger-Ellison syndrome have been treated continuously for up to one year
Adolescents 12 Years of Age and Older
Symptomatic GERD  20 mg once daily Up to 8 weeks

* For those patients who have not healed after 8 weeks of treatment, an additional 8-week course of Aciphex may be considered.
** If symptoms do not resolve completely after 4 weeks, an additional course of treatment may be considered.
*** Most patients heal within 4 weeks; some patients may require additional therapy to achieve healing.

Administration Instructions 

  • Swallow Aciphex delayed-release tablets whole.  Do not chew, crush, or split tablets.
  • For the treatment of duodenal ulcers take Aciphex delayed-release tablets after a meal.
  • For Helicobacter pylori eradication take Aciphex delayed-release tablets with food.
  • For all other indications Aciphex delayed-release tablets can be taken with or without food.
  • Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and go back to the normal schedule. Do not take two doses at the same time.

Adverse reactions

The following serious adverse reactions are described below and elsewhere in labeling:

  • Acute Interstitial Nephritis [see Warnings and Precautions (5.3)]
  • Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.4)]
  • Bone Fracture [see Warnings and Precautions (5.5)]
  • Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.6)]
  • Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.7)]
  • Hypomagnesemia [see Warnings and Precautions (5.8)]

6.1 Clinical Studies Experience

Because clinical trials are conducted under varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adults

The data described below reflect exposure to Aciphex delayed-release tablets in 1064 adult patients exposed for up to 8 weeks.  The studies were primarily placebo- and active-controlled trials in adult patients with Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD), Duodenal Ulcers and Gastric Ulcers.  The population had a mean age of 53 years (range 18-89 years) and had a ratio of approximately 60% male: 40% female.  The racial distribution was 86% Caucasian, 8% African American, 2% Asian, and 5% other.  Most patients received either 10 mg, 20 mg or 40 mg per day of Aciphex delayed-release tablets. 

An analysis of adverse reactions appearing in ≥2% of patients treated with Aciphex delayed-release tablets (n=1064) and with a greater frequency than placebo (n=89) in controlled North American and European acute treatment trials, revealed the following adverse reactions:  pain (3% vs. 1%), pharyngitis (3% vs. 2%), flatulence (3% vs. 1%), infection (2% vs. 1%), and constipation (2% vs. 1%). 

Three long-term maintenance studies consisted of a total of 740 adult patients; at least 54% of adult patients were exposed to Aciphex delayed-release tablets for 6 months and at least 33% were exposed for 12 months.  Of the 740 adult patients, 247 (33%) and 241 (33%) patients received 10 mg and 20 mg of Aciphex delayed-release tablets, respectively, while 169 (23%) patients received placebo and 83 (11%) received omeprazole.

The safety profile of rabeprazole in the maintenance studies in adults was consistent with what was observed in the acute studies.

Less common adverse reactions seen in controlled clinical trials (<2% of patients treated with Aciphex delayed-release tablets and greater than placebo) and for which there is a possibility of a causal relationship to rabeprazole, include the following:  headache, abdominal pain, diarrhea, dry mouth, dizziness, peripheral edema, hepatic enzyme increase, hepatitis, hepatic encephalopathy, myalgia, and arthralgia.

Combination Treatment with Amoxicillin and Clarithromycin:  In clinical trials using combination therapy with rabeprazole plus amoxicillin and clarithromycin (RAC), no adverse reactions unique to this drug combination were observed.  In the U.S. multicenter study, the most frequently reported drug related adverse reactions for patients who received RAC therapy for 7 or 10 days were diarrhea (8% and 7%) and taste perversion (6% and 10%), respectively.

No clinically significant laboratory abnormalities particular to the drug combinations were observed.

For more information on adverse reactions or laboratory changes with amoxicillin or clarithromycin, refer to their respective prescribing information, Adverse Reactions section.

Pediatrics

In a multicenter, open-label study of adolescent patients 12 to 16 years of age with a clinical diagnosis of symptomatic GERD or endoscopically proven GERD, the adverse event profile was similar to that of adults.  The adverse reactions reported without regard to relationship to Aciphex delayed-release tablets that occurred in ≥2% of 111 patients were headache (9.9%), diarrhea (4.5%), nausea (4.5%), vomiting (3.6%), and abdominal pain (3.6%).  The related reported adverse reactions that occurred in ≥2% of patients were headache (5.4%) and nausea (1.8%).  There were no adverse reactions reported in this study that were not previously observed in adults.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post approval use of rabeprazole.  Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:  sudden death; coma; hyperammonemia; jaundice; rhabdomyolysis; disorientation and delirium; anaphylaxis; angioedema; systemic lupus erythematosus, bullous and other drug eruptions of the skin; severe dermatologic reactions, including toxic epidermal necrolysis (some fatal), Stevens-Johnson syndrome, cutaneous lupus erythematosus and erythema multiforme; interstitial pneumonia; interstitial nephritis; TSH elevations; bone fractures; hypomagnesemia and Clostridium difficile-associated diarrhea.  In addition, agranulocytosis, hemolytic anemia, leukopenia, pancytopenia, and thrombocytopenia have been reported.  Increases in prothrombin time/INR in patients treated with concomitant warfarin have been reported.

Clinical studies

14.1 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 Aciphex 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:

Table 7: Healing of Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD) Percentage of Patients Healed
Week Aciphex delayed-release tablets Placebo
N=25
10 mg once daily
N=27
20 mg once daily
N=25
40 mg once daily
N=26
4 63%* 56%* 54%* 0%
8 93%* 84%* 85%* 12%

* (p<0.001 versus placebo)

In addition, there was a statistically significant difference in favor of the Aciphex 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 Aciphex 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 Aciphex 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 Aciphex delayed-release tablets compared to ranitidine: 

Table 8: Healing Of Erosive Or Ulcerative Gastroesophageal Reflux Disease (GERD) Percentage of Patients Healed
Week 20 mg Aciphex delayed-release tablets once daily
N=167
Ranitidine 150 mg four times daily
N=169
4 59%* 36%
8 87%* 66%

* (p<0.001 versus ranitidine)

A dose of 20 mg once daily of Aciphex 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).  Aciphex 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 Aciphex delayed-release tablets is 20 mg once daily for 4 to 8 weeks.

14.2 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 Aciphex delayed-release tablets once daily or placebo.  As demonstrated in Tables 10 and 11 below, patients treated with Aciphex 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 Aciphex delayed-release tablets is 20 mg once daily.

Table 9: Percent of Patients in Endoscopic Remission
Aciphex delayed-release tablets Placebo
10 mg once daily 20 mg once daily
Study 1 N=66 N=67 N=70
Week 4 83%* 96%* 44%
Week 13 79%* 93%* 39%
Week 26 77%* 93%* 31%
Week 39 76%* 91%* 30%
Week 52 73%* 90%* 29%
Study 2 N=93 N=93 N=99
Week 4 89%* 94%* 40%
Week 13 86%* 91%* 33%
Week 26 85%* 89%* 30%
Week 39 84%* 88%* 29%
Week 52 77%* 86%* 29%
COMBINED STUDIES N=159 N=160 N=169
Week 4 87%* 94%* 42%
Week 13 83%* 92%* 36%
Week 26 82%* 91%* 31%
Week 39 81%* 89%* 30%
Week 52 75%* 87%* 29%

* (p<0.001 versus placebo)

Table 10: Percent of Patients Without Relapse in Heartburn Frequency and Daytime and Nighttime Heartburn Severity at Week 52
Aciphex delayed-release tablets Placebo
10 mg once daily 20 mg once daily
Heartburn Frequency
Study 1 46/55 (84%)* 48/52 (92%)* 17/45 (38%)
Study 2 50/72 (69%)* 57/72 (79%)* 22/79 (28%)
Daytime Heartburn Severity
Study 1 61/64 (95%)* 60/62 (97%)* 42/61 (69%)
Study 2 73/84 (87%)† 82/87 (94%)* 67/90 (74%)
Nighttime Heartburn
Severity
Study 1 57/61 (93%)* 60/61 (98%)* 37/56 (66%)
Study 2 67/80 (84%) 79/87 (91%)† 64/87 (74%)

* p≤0.001 versus placebo
† 0.001<p<0.05 versus placebo

14.3 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 20 mg Aciphex delayed-release tablets 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 Aciphex 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.

Figure 2:  Mean Daytime Heartburn Scores RAB-USA-2

Figure 3:  Mean Nighttime Heartburn Scores RAB-USA-2

Figure 4:  Mean Daytime Heartburn Scores RAB-USA-3

Figure 5:  Mean Nighttime Heartburn Scores RAB-USA-3

           

In addition, the combined analysis of these two studies showed 20 mg of Aciphex 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 Aciphex delayed-release tablets also significantly reduced daily antacid consumption versus placebo over 4 weeks (p<0.001).

The recommended dosage of Aciphex delayed-release tablets is 20 mg once daily for 4 weeks.

14.4 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 Aciphex delayed-release tablets once daily versus placebo for healing endoscopically defined duodenal ulcers, 100 patients were treated for up to four weeks.  Aciphex was significantly superior to placebo in producing healing of duodenal ulcers.  The percentages of patients with endoscopic healing are presented below:

Table 11: Healing of Duodenal Ulcers Percentage of Patients Healed
Week Aciphex delayed-release tablets Placebo
N=33
20 mg once
daily
N=34
40 mg once daily
N=33
2 44% 42% 21%
4 79%* 91%* 39%

* p≤0.001 versus placebo

At Weeks 2 and 4, significantly more patients in the Aciphex 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 Aciphex 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 Aciphex 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 Aciphex 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 Aciphex 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, Aciphex was comparable to omeprazole in producing healing of duodenal ulcers.  The percentages of patients with endoscopic healing at two and four weeks are presented below:

Table 12: Healing of Duodenal Ulcers Percentage of Patients Healed
Week Aciphex delayed-release tablets
20 mg once daily
N=102
Omeprazole
20 mg once daily
N=103
95% Confidence Interval for the
Treatment Difference
(Aciphex - Omeprazole)
2 69% 61% (–6%, 22%)
4 98% 93% (–3%, 15%)

Aciphex and omeprazole were comparable in providing complete resolution of symptoms.

The recommended dosage of Aciphex delayed-release tablets is 20 mg once daily for 4 weeks.

14.5 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 Aciphex 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.

Table 13: Helicobacter pylori Eradication at ≥6 Weeks After the End of Treatment

Treatment Group
Percent (%) of Patients Cured
(Number of Patients)
Difference
(RAC – OAC)
[95% Confidence Interval]
7-day RAC* 10-day OAC
Per Protocola 84.3%
(N=166)
81.6%
(N=179)
2.8
[- 5.2, 10.7]
Intent-to-Treatb 77.3%
(N=194)
73.3%
(N=206)
4.0
[- 4.4, 12.5]
10-day RAC* 10-day OAC
Per Protocola 86.0%
(N=171)
81.6%
(N=179)
4.4
[- 3.3, 12.1]
Intent-to-Treatb 78.1%
(N=196)
73.3%
(N=206)
4.8
[- 3.6, 13.2]
3-day RAC 10-day OAC
Per Protocola 29.9%
(N=167)
81.6%
(N=179)
- 51.6
[- 60.6, - 42.6]
Intent-to-Treatb 27.3%
(N=187)
73.3%
(N=206)
- 46.0
[- 54.8, - 37.2]

a Patients were included in the analysis if they had H. pylori infection documented at baseline, defined as a positive 13C-UBT plus rapid urease test or culture and were not protocol violators.  Patients who dropped out of the study due to an adverse event related to the study drug were included in the evaluable analysis as failures of therapy.
b Patients were included in the analysis if they had documented H. pylori infection at baseline as defined above and took at least one dose of study medication.  All dropouts were included as failures of therapy.
* The 95% confidence intervals for the difference in eradication rates for 7-day RAC minus 10-day RAC are (- 9.3, 6.0) in the PP population and (-9.0, 7.5) in the ITT population.

The recommended dosage of Aciphex delayed-release tablets is 20 mg twice daily with amoxicillin and clarithromycin for 7 days.

14.6 Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome in Adults

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

The recommended starting dosage of Aciphex delayed-release tablets is 60 mg once daily.

Aciphex Dosage

Take Aciphex exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. Your doctor will determine the right dose for you based on your medical condition.

The recommended dose for Aciphex is 20 mg once daily for 4 to 8 weeks. Your doctor will tell you how long to take Aciphex.

Dosing & Uses

Dosage Forms & Strengths

tablet, delayed-release

  • 20mg

Duodenal Ulcer

Indicated for short-term (up to 4 weeks) treatment in healing and symptomatic relief of duodenal ulcers

20 mg PO qDay after morning meal for up to 4 weeks; to achieve healing, some patients may require additional therapy

Helicobacter Pylori Eradication

In combination with amoxicillin and clarithromycin for treatment of H pylori infection and duodenal ulcer disease (active or history within past 5 yr)

20 mg PO BID for 7 days with morning and evening meals; take with amoxicillin 1000 mg PO BID and clarithromycin 500 mg BID

Gastroesophageal Reflux Disease

Healing or erosive or ulcerative GERD

  • 20 mg PO qDay for 4-8 weeks; if not healed after 8 weeks, an additional 8-week course may be considered
  • Maintenance dosing (20 mg/day for up to 12 months) shown to reduce relapse rates

Symptomatic GERD

  • Treatment of daytime and nighttime heartburn and other symptoms associated with GERD
  • 20 mg PO qDay for 4 weeks; if symptoms not completely resolved after 4 weeks, an additional course may be considered

Hypersecretory Conditions

Long-term treatment of pathologic hypersecretory conditions, including Zollinger-Ellison syndrome

60 mg PO qDay initially; may increase to 100 mg PO qDay or 60 mg PO q12hr

Dosing considerations

  • Continue use as long as clinically needed; some patients with SE have been treated continuously for up to 1 yr

Dosage Modifications

Renal impairment: Dose adjustment not necessary

Hepatic impairment

  • Mild to moderate: Dose adjustment not necessary
  • Severe: Not studied

Dosage Forms & Strengths

tablet, delayed-release

  • 20mg

capsule, sprinkle

  • 5mg
  • 10mg

Gastroesophageal Reflux Disease

Delayed-release tablet

  • Indicated for short-term treatment of symptomatic GERD in adolescents
  • <12 years: Safety and efficacy not established
  • ≥12 years: 20 mg PO qDay for up to 8 weeks

Delayed-release capsule (sprinkles)

  • <1 year: Safety and efficacy not established
  • 1-11 years (<15 kg): 5 mg PO qDay 30 minutes before a meal, for up to 12 weeks; may increase to 10 mg/day if inadequate response
  • 1-11 years (≥15 kg): 10 mg PO qDay 30 minutes before a meal, for up to 12 weeks

Important information

You should not use AcipHex if you are allergic to rabeprazole or to similar medicines such as lansoprazole (Prevacid), esomeprazole (Nexium), omeprazole (Prilosec, Zegerid), or pantoprazole (Protonix). AcipHex is not for immediate relief of heartburn symptoms.

Some conditions are treated with a combination of AcipHex and antibiotics. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice.

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 AcipHex 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.

Before taking this medicine

Heartburn is often confused with the first symptoms of a heart attack. Seek emergency medical attention if you have chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, and a general ill feeling.

You should not use AcipHex if you are allergic to rabeprazole or:

  • if you also take any medicine that contains rilpivirine, such as Edurant or Complera; or

  • if you also allergic to medicines like rabeprazole, such as esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec, Zegerid), or pantoprazole (Protonix).

To make sure AcipHex is safe for you, tell your doctor if you have:

  • liver disease;

  • osteoporosis or low bone mineral density (osteopenia);

  • lupus (an autoimmune disorder); or

  • low levels of magnesium in your blood.

Taking a proton pump inhibitor such as AcipHex may increase your risk of bone fracture in the hip, wrist, or spine. This effect has occurred mostly in people who have taken the medicine long term or more than once per day, and in those who are age 50 and older. It is not clear whether AcipHex is the actual cause of an increased risk of fracture.

It is not known whether AcipHex will harm an unborn baby. Tell your doctor if you are pregnant.

It is not known whether rabeprazole passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Rabeprazole Identification

Substance Name

Rabeprazole

CAS Registry Number

117976-89-3

Drug Class

Anti-Ulcer Agents

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