Drug Detail:Aciphex (Rabeprazole [ ra-bep-ra-zole ])
Drug Class: Proton pump inhibitors
Highlights of Prescribing Information
ACIPHEX® (rabeprazole sodium) delayed-release tablets, for oral use
Initial U.S. Approval: 1999
Recent Major Changes
| Warnings and Precautions, | |
| Severe Cutaneous Adverse Reactions (5.6) | 03/2022 |
| Hypomagnesemia and Mineral Metabolism (5.9) | 03/2022 |
Indications and Usage for Aciphex
ACIPHEX delayed-release tablets is a proton pump inhibitor (PPI) indicated in adults for:
- Healing of Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD) (1.1).
- Maintenance of Healing of Erosive or Ulcerative GERD (1.2).
- Treatment of Symptomatic GERD (1.3).
- Healing of Duodenal Ulcers (1.4).
- Helicobacter pylori Eradication to Reduce Risk of Duodenal Ulcer Recurrence (1.5).
- Treatment of Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome (1.6).
In adolescent patients 12 years of age and older for:
- Short-term Treatment of Symptomatic GERD (1.7).
Aciphex Dosage and Administration
| Indication | Recommended Dosage (2) |
|---|---|
| Healing of Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD) | 20 mg once daily for 4 to 8 weeks |
| Maintenance of Healing of Erosive or Ulcerative GERD* studied for 12 months | 20 mg once daily* |
| Symptomatic GERD in Adults | 20 mg once daily for 4 weeks |
| Healing of Duodenal Ulcers | 20 mg once daily after morning meal for up to 4 weeks |
| Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Three Drug Regimen: | |
| ACIPHEX 20 mg Amoxicillin 1000 mg Clarithromycin 500 mg | All three medications should be taken twice daily with morning and evening meals for 7 days |
| Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome | Starting dose 60 mg once daily then adjust to patient needs |
| Symptomatic GERD in Adolescents 12 Years of Age and Older | 20 mg once daily for up to 8 weeks |
Administration Instructions (2):
- Swallow ACIPHEX delayed-release tablets whole. Do not chew, crush or split the 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.
Dosage Forms and Strengths
Delayed-Release Tablets: 20 mg (3).
Contraindications
- Patients with a history of hypersensitivity to rabeprazole (4).
- PPIs, including ACIPHEX delayed-release tablets, are contraindicated in patients receiving rilpivirine-containing products (4, 7).
- Refer to the Contraindications section of the prescribing information for clarithromycin and amoxicillin, when administered in combination with ACIPHEX (4).
Warnings and Precautions
- Gastric Malignancy: In adults, symptomatic response to therapy with rabeprazole does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing (5.1).
- Use with Warfarin: Monitor for increases in INR and prothrombin time (5.2, 7).
- Acute Tubulointerstitial Nephritis: Discontinue treatment and evaluate patients (5.3).
- Clostridium difficile-Associated Diarrhea: PPI therapy may be associated with increased risk of (5.4).
- Bone Fracture: Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine (5.5).
- Severe Cutaneous Adverse Reactions: Discontinue at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation (5.6).
- Cutaneous and Systemic Lupus Erythematosus: Mostly cutaneous, new onset or exacerbation of existing disease; discontinue ACIPHEX and refer to specialist for evaluation (5.7).
- Cyanocobalamin (Vitamin B-12) Deficiency: Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin (5.8).
- Hypomagnesemia and Mineral Metabolism: Reported rarely with prolonged treatment with PPIs (5.9).
- Interaction with Methotrexate: Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. With high dose methotrexate administration, consider a temporary withdrawal of ACIPHEX delayed-release tablets (5.10, 7).
- Fundic Gland Polyps: Risk increases with long-term use, especially beyond one year. Use the shortest duration of therapy (5.11).
Adverse Reactions/Side Effects
- Most common adverse reactions in adults (>2%) are pain, pharyngitis, flatulence, infection, and constipation (6.1).
- Most common adverse reactions in adolescents (≥2%) are headache, diarrhea, nausea, vomiting, and abdominal pain (6.1).
To report SUSPECTED ADVERSE REACTIONS, contact Woodward Pharma Services LLC at 1-844-944-0912 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
Drug Interactions
See full prescribing information for a list of clinically important drug interactions (7).
Use In Specific Populations
Pediatric Use: Dosage strength not appropriate for patients less than 12 years (2, 8.4).
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 3/2022
Full Prescribing Information
1. Indications and Usage for Aciphex
1.1 Healing of Erosive or Ulcerative GERD in Adults
ACIPHEX 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 ACIPHEX may be considered.
1.2 Maintenance of Healing of Erosive or Ulcerative GERD in Adults
ACIPHEX 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.
1.3 Treatment of Symptomatic GERD in Adults
ACIPHEX 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.
1.4 Healing of Duodenal Ulcers in Adults
ACIPHEX 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.
1.5 Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence in Adults
ACIPHEX 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].
2. Aciphex 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.
| 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 |
3. Dosage Forms and Strengths
ACIPHEX delayed-release tablets are provided in one strength, 20 mg. The tablets are round, light yellow, enteric coated, biconvex tablets. "ACIPHEX 20" is imprinted in red on one side of the tablet.
4. Contraindications
- ACIPHEX 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 [see Warnings and Precautions (5.3), Adverse Reactions (6)].
- PPIs, including ACIPHEX, are contraindicated with rilpivirine-containing products [see Drug Interactions (7)].
- For information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with ACIPHEX delayed-release tablets, refer to the Contraindications section of their package inserts.
5. Warnings and Precautions
5.1 Presence of Gastric Malignancy
In adults, symptomatic response to therapy with ACIPHEX does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI.
5.2 Interaction 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 ACIPHEX delayed-release tablets and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time [see Drug Interactions (7)].
5.3 Acute Tubulointerstitial Nephritis
Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions, to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia).
Discontinue ACIPHEX and evaluate patients with suspected acute TIN [see Contraindication (4)].
5.4 Clostridium difficile-Associated Diarrhea
Published observational studies suggest that PPI therapy like ACIPHEX 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 [see Adverse Reactions (6.2)].
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. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with ACIPHEX, refer to Warnings and Precautions sections of the corresponding prescribing information.
5.5 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 [see Dosage and Administration (2), Adverse Reactions (6.2)].
5.6 Severe Cutaneous Adverse Reactions
Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs [see Adverse Reactions (6.2)]. Discontinue ACIPHEX at first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.
5.7 Cutaneous and Systemic Lupus Erythematosus
Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including rabeprazole. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematosus cases were CLE.
The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement.
Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported.
Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving ACIPHEX, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g. ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations.
5.8 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 in patients treated with ACIPHEX.
5.9 Hypomagnesemia and Mineral Metabolism
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. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. 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), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2)].
Consider monitoring magnesium and calcium levels prior to initiation of ACIPHEX and periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism). Supplement with magnesium and/or calcium as necessary. If hypocalcemia is refractory to treatment, consider discontinuing the PPI.
5.10 Interaction with Methotrexate
Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum concentrations 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 [see Drug Interactions (7)].
5.11 Fundic Gland Polyps
PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated.
6. Adverse Reactions/Side Effects
The following serious adverse reactions are described below and elsewhere in labeling:
- Acute Tubulointerstitial 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 (5.7)]
- Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.8)]
- Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions (5.9)]
- Fundic Gland Polyps [see Warnings and Precautions (5.11)]
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.
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:
Blood and Lymphatic System Disorders: agranulocytosis, hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia
Ear and Labyrinth Disorders: vertigo
Eye Disorders: blurred vision
Gastrointestinal Disorders: fundic gland polyps
General Disorders and Administration Site Conditions: sudden death
Hepatobiliary Disorders: jaundice
Immune System Disorders: anaphylaxis, angioedema, systemic lupus erythematosus, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal), DRESS, AGEP
Infections and Infestations: Clostridium difficile-associated diarrhea
Investigations: Increases in prothrombin time/INR (in patients treated with concomitant warfarin), TSH elevations
Metabolism and Nutrition Disorders: hyperammonemia, hypomagnesemia, hypocalcemia, hypokalemia [Warnings and Precautions 5.8], hyponatremia
Musculoskeletal System Disorders: bone fracture, rhabdomyolysis
Nervous System Disorders: coma
Psychiatric Disorders: delirium, disorientation
Renal and Urinary Disorders: interstitial nephritis
Respiratory, Thoracic and Mediastinal Disorders: interstitial pneumonia
Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions including bullous and other drug eruptions of the skin, cutaneous lupus erythematosus, erythema multiforme
7. Drug Interactions
Table 2 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with ACIPHEX delayed-release tablets and instructions for preventing or managing them.
Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs.
| Antiretrovirals | |
| Clinical Impact: | The effect of PPI on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known.
|
| Intervention: | Rilpivirine-containing products: Concomitant use with ACIPHEX delayed-release tablets is contraindicated [see Contraindications (4)]. See prescribing information. Atazanavir: See prescribing information for atazanavir for dosing information. Nelfinavir: Avoid concomitant use with ACIPHEX delayed-release tablets. See prescribing information for nelfinavir. Saquinavir: See the prescribing information for saquinavir and monitor for potential saquinavir toxicities. Other antiretrovirals: See prescribing information. |
| Warfarin | |
| Clinical Impact: | Increased INR and prothrombin time in patients receiving PPIs, including rabeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death [see Warnings and Precautions (5.2)]. |
| Intervention: | Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range. See prescribing information for warfarin. |
| Methotrexate | |
| Clinical Impact: | Concomitant use of rabeprazole with methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of methotrexate with PPIs have been conducted [see Warnings and Precautions (5.9)]. |
| Intervention: | A temporary withdrawal of ACIPHEX delayed-release tablets may be considered in some patients receiving high dose methotrexate administration. |
| Digoxin | |
| Clinical Impact: | Potential for increased exposure of digoxin [see Clinical Pharmacology (12.3)]. |
| Intervention: | Monitor digoxin concentrations. Dose adjustment of digoxin may be needed to maintain therapeutic drug concentrations. See prescribing information for digoxin. |
| Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole, itraconazole) | |
| Clinical Impact: | Rabeprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity. |
| Intervention: | Mycophenolate mofetil (MMF): 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 ACIPHEX delayed-release tablets and MMF. Use ACIPHEX delayed-release tablets with caution in transplant patients receiving MMF. See the prescribing information for other drugs dependent on gastric pH for absorption. |
| Combination Therapy with Clarithromycin and Amoxicillin | |
| Clinical Impact: | Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and are contraindicated. Amoxicillin also has drug interactions. |
| Intervention: | See Contraindications and Warnings and Precautions in prescribing information for clarithromycin. See Drug Interactions in prescribing information for amoxicillin. |
| Tacrolimus | |
| Clinical Impact: | Potentially increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19. |
| Intervention: | Monitor tacrolimus whole blood trough concentrations. Dose adjustment of tacrolimus may be needed to maintain therapeutic drug concentrations. See prescribing information for tacrolimus. |
| Interactions with Investigations of Neuroendocrine Tumors | |
| Clinical Impact: | Serum chromogranin A (CgA) levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. |
| Intervention: | Temporarily stop ACIPHEX delayed-release tablets treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary. |
| Interaction with Secretin Stimulation Test | |
| Clinical Impact: | Hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma. |
| Intervention: | Temporarily stop treatment with ACIPHEX delayed-release tablets at least 14 days before assessing to allow gastrin levels to return to baseline. |
| False Positive Urine Tests for THC | |
| Clinical Impact: | There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs. |
| Intervention: | An alternative confirmatory method should be considered to verify positive results. |
8. Use In Specific Populations
8.4 Pediatric Use
The safety and effectiveness of ACIPHEX delayed-release tablets have been established in pediatric patients for adolescent patients 12 years of age and older for the treatment of symptomatic GERD. Use of ACIPHEX delayed-release tablets in this age group is supported by adequate and well controlled studies in adults and a multicenter, randomized, open-label, parallel-group study in 111 adolescent patients 12 to 16 years of age. Patients had a clinical diagnosis of symptomatic GERD, or suspected or endoscopically proven GERD and were randomized to either 10 mg or 20 mg once daily for up to 8 weeks for the evaluation of safety and efficacy. The adverse reaction profile in adolescent patients was similar to that of adults. The related reported adverse reactions that occurred in ≥2% of patients were headache (5%) and nausea (2%). There were no adverse reactions reported in these studies that were not previously observed in adults.
The safety and effectiveness of ACIPHEX delayed-release tablets have not been established in pediatric patients for:
- Healing of Erosive or Ulcerative GERD
- Maintenance of Healing of Erosive or Ulcerative GERD
- Treatment of Symptomatic GERD
- Healing of Duodenal Ulcers
- Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence
- Treatment of Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome
ACIPHEX delayed-release 20 mg tablets are not recommended for use in pediatric patients less than 12 years of age because the tablet strength exceeds the recommended dose for these patients [see Dosage and Administration (2)]. For pediatric patients 1 year to less than 12 years of age consider another rabeprazole formulation. The safety and effectiveness of a different dosage form and dosage strength of rabeprazole has been established in pediatric patients 1 to 11 years for the treatment of GERD.
8.5 Geriatric Use
Of the total number of subjects (n=2009) in clinical studies of ACIPHEX delayed-release tablets, 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.
8.6 Hepatic Impairment
Administration of ACIPHEX delayed-release tablets to patients with mild to moderate hepatic impairment (Child-Pugh Class A and B, respectively) resulted in increased exposure and decreased elimination [see Clinical Pharmacology (12.3)]. No dosage adjustment is necessary in patients with mild to moderate hepatic impairment. There is no information in patients with severe hepatic impairment (Child-Pugh Class C). Avoid use of ACIPHEX delayed-release tablets in patients with severe hepatic impairment; however, if treatment is necessary, monitor patients for adverse reactions [see Warnings and Precautions (5), Adverse Reactions (6)].
10. Overdosage
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 once daily. 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.
If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.
11. Aciphex Description
The active ingredient in ACIPHEX delayed-release tablets is rabeprazole sodium, which is a proton pump inhibitor. It is a substituted benzimidazole known chemically as 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]-methyl]sulfinyl]-1H–benzimidazole sodium salt. It has an empirical formula of C18H20N3NaO3S and a molecular weight of 381.42. Rabeprazole sodium is a white to slightly yellowish-white solid. It is very soluble in water and methanol, freely soluble in ethanol, chloroform, and ethyl acetate and insoluble in ether and n-hexane. The stability of rabeprazole sodium is a function of pH; it is rapidly degraded in acid media, and is more stable under alkaline conditions. The structural figure is:
Figure 1
ACIPHEX is available for oral administration as delayed-release, enteric-coated tablets containing 20 mg of rabeprazole sodium.
Inactive ingredients of the 20 mg tablet are carnauba wax, crospovidone, diacetylated monoglycerides, ethylcellulose, hydroxypropyl cellulose, hypromellose phthalate, magnesium stearate, mannitol, sodium hydroxide, sodium stearyl fumarate, talc, and titanium dioxide. Iron oxide yellow is the coloring agent for the tablet coating. Iron oxide red is the ink pigment.
12. Aciphex - Clinical Pharmacology
12.1 Mechanism of Action
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 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. It inhibits acid transport in porcine gastric vesicles with a half-life of 90 seconds.
12.2 Pharmacodynamics
Antisecretory Activity
The antisecretory effect begins within one hour after oral administration of 20 mg ACIPHEX delayed-release tablets. The median inhibitory effect of rabeprazole on 24 hour gastric acidity is 88% of maximal after the first dose. A 20 mg dose of ACIPHEX delayed-release tablets inhibits basal and peptone meal-stimulated acid secretion versus placebo by 86% and 95%, respectively, and increases the percent of a 24-hour period that the gastric pH>3 from 10% to 65% (see table below). This relatively prolonged pharmacodynamic action compared to the short pharmacokinetic half-life (1 to 2 hours) reflects the sustained inactivation of the H+, K+ATPase.
| Parameter | ACIPHEX delayed-release tablets (20 mg once daily) | Placebo |
|---|---|---|
|
||
| Basal Acid Output (mmol/hr) | 0.4* | 2.8 |
| Stimulated Acid Output (mmol/hr) | 0.6* | 13.3 |
| % Time Gastric pH>3 | 65* | 10 |
Compared to placebo, 10 mg, 20 mg, and 40 mg of ACIPHEX delayed-release tablets, administered once daily for 7 days significantly decreased intragastric acidity with all doses for each of four meal-related intervals and the 24-hour time period overall. In this study, there were no statistically significant differences between doses; however, there was a significant dose-related decrease in intragastric acidity. The ability of rabeprazole to cause a dose-related decrease in mean intragastric acidity is illustrated below.
| ACIPHEX delayed-release tablets | ||||
|---|---|---|---|---|
| AUC interval (hrs) | 10 mg (N=24) | 20 mg (N=24) | 40 mg (N=24) | Placebo (N=24) |
|
||||
| 08:00 – 13:00 | 19.6±21.5* | 12.9±23* | 7.6±14.7* | 91.1±39.7 |
| 13:00 – 19:00 | 5.6±9.7* | 8.3±29.8* | 1.3±5.2* | 95.5±48.7 |
| 19:00 – 22:00 | 0.1±0.1* | 0.1±0.06* | 0.0±0.02* | 11.9±12.5 |
| 22:00 – 08:00 | 129.2±84* | 109.6±67.2* | 76.9±58.4* | 479.9±165 |
| AUC 0-24 hours | 155.5±90.6* | 130.9±81* | 85.8±64.3* | 678.5±216 |
After administration of 20 mg ACIPHEX delayed-release tablets once daily for eight days, the mean percent of time that gastric pH greater than 3 or gastric pH greater than 4 after a single dose (Day 1) and multiple doses (Day 8) was significantly greater than placebo (see table below). The decrease in gastric acidity and the increase in gastric pH observed with 20 mg ACIPHEX delayed-release tablets administered once daily for eight days were compared to the same parameters for placebo, as illustrated below:
| ACIPHEX delayed-release tablets 20 mg once daily | Placebo | |||
|---|---|---|---|---|
| Parameter | Day 1 | Day 8 | Day 1 | Day 8 |
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| Mean AUC0-24 Acidity | 340.8* | 176.9* | 925.5 | 862.4 |
| Median trough pH (23-hr)† | 3.77 | 3.51 | 1.27 | 1.38 |
| % Time Gastric pH greater than 3‡ | 54.6* | 68.7* | 19.1 | 21.7 |
| % Time Gastric pH greater than 4‡ | 44.1* | 60.3* | 7.6 | 11.0 |
12.3 Pharmacokinetics
After oral administration of 20 mg ACIPHEX delayed-release tablets, peak plasma concentrations (Cmax) of rabeprazole occur over a range of 2 to 5 hours (Tmax). The rabeprazole Cmax and AUC are linear over an oral dose range of 10 mg to 40 mg. There is no appreciable accumulation when doses of 10 mg to 40 mg are administered every 24 hours; the pharmacokinetics of rabeprazole is not altered by multiple dosing.
Drug Interaction Studies
12.4 Microbiology
The following in vitro data are available but the clinical significance is unknown.
Rabeprazole sodium, amoxicillin and clarithromycin as a three drug regimen has been shown to be active against most strains of Helicobacter pylori in vitro and in clinical infections [see Indications and Usage (1), Clinical Studies (14.5)].
12.5 Pharmacogenomics
In a clinical study in evaluating ACIPHEX delayed-release tablets in Japanese 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. The clinical relevance of this is not known. 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.
13. Nonclinical Toxicology
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
In an 88/104-week carcinogenicity study in CD-1 mice, rabeprazole at oral doses up to 100 mg/kg/day did not produce any increased tumor occurrence. The highest tested dose produced a systemic exposure to rabeprazole (AUC) of 1.40 µg∙hr/mL which is 1.6 times the human exposure (plasma AUC0-∞ = 0.88 µg∙hr/mL) at the recommended dose for GERD (20 mg/day). In a 28-week carcinogenicity study in p53+/- transgenic mice, rabeprazole at oral doses of 20, 60, and 200 mg/kg/day did not cause an increase in the incidence rates of tumors but produced gastric mucosal hyperplasia at all doses. The systemic exposure to rabeprazole at 200 mg/kg/day is about 17 to 24 times the human exposure at the recommended dose for GERD. In a 104-week carcinogenicity study in Sprague-Dawley rats, males were treated with oral doses of 5, 15, 30 and 60 mg/kg/day and females with 5, 15, 30, 60, and 120 mg/kg/day. Rabeprazole produced gastric enterochromaffin-like (ECL) cell hyperplasia in male and female rats and ECL cell carcinoid tumors in female rats at all doses including the lowest tested dose. The lowest dose (5 mg/kg/day) produced a systemic exposure to rabeprazole (AUC) of about 0.1 µg∙hr/mL which is about 0.1 times the human exposure at the recommended dose for GERD. In male rats, no treatment related tumors were observed at doses up to 60 mg/kg/day producing a rabeprazole plasma exposure (AUC) of about 0.2 µg∙hr/mL (0.2 times the human exposure at the recommended dose for GERD).
Rabeprazole was positive in the Ames test, the Chinese hamster ovary cell (CHO/HGPRT) forward gene mutation test, and the mouse lymphoma cell (L5178Y/TK+/–) forward gene mutation test. Its demethylated-metabolite was also positive in the Ames test. Rabeprazole was negative in the in vitro Chinese hamster lung cell chromosome aberration test, the in vivo mouse micronucleus test, and the in vivo and ex vivo rat hepatocyte unscheduled DNA synthesis (UDS) tests.
Rabeprazole at intravenous doses up to 30 mg/kg/day (plasma AUC of 8.8 µg∙hr/mL, about 10 times the human exposure at the recommended dose for GERD) was found to have no effect on fertility and reproductive performance of male and female rats.
14. 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:
| ACIPHEX delayed-release tablets | ||||
|---|---|---|---|---|
| Week | 10 mg once daily N=27 | 20 mg once daily N=25 | 40 mg once daily N=26 | Placebo N=25 |
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| 4 | 63%* | 56%* | 54%* | 0% |
| 8 | 93%* | 84%* | 85%* | 12% |
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 statistically superior in the patients treated with ACIPHEX delayed-release tablets compared to ranitidine:
| Week | 20 mg ACIPHEX delayed-release tablets once daily N=167 | Ranitidine 150 mg four times daily N=169 |
|---|---|---|
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| 4 | 59%* | 36% |
| 8 | 87%* | 66% |
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.
| ACIPHEX delayed-release tablets | Placebo | ||
|---|---|---|---|
| 10 mg once daily | 20 mg once daily | ||
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| 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% |
| ACIPHEX delayed-release tablets | Placebo | ||
|---|---|---|---|
| 10 mg once daily | 20 mg once daily | ||
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| 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%) |
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.
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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:
| ACIPHEX delayed-release tablets | Placebo N=33 |
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| Week | 20 mg once daily N=34 | 40 mg once daily N=33 | |
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| 2 | 44% | 42% | 21% |
| 4 | 79%* | 91%* | 39% |
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:
| 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.
| Treatment Group Percent (%) of Patients Cured (Number of Patients) | Difference (RAC – OAC) [95% Confidence Interval] |
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| 7-day RAC* | 10-day OAC | ||
| Per Protocol† | 84.3% (N=166) | 81.6% (N=179) | 2.8 [- 5.2, 10.7] |
| Intent-to-Treat‡ | 77.3% (N=194) | 73.3% (N=206) | 4.0 [- 4.4, 12.5] |
| 10-day RAC* | 10-day OAC | ||
| Per Protocol† | 86.0% (N=171) | 81.6% (N=179) | 4.4 [- 3.3, 12.1] |
| Intent-to-Treat‡ | 78.1% (N=196) | 73.3% (N=206) | 4.8 [- 3.6, 13.2] |
| 3-day RAC | 10-day OAC | ||
| Per Protocol† | 29.9% (N=167) | 81.6% (N=179) | - 51.6 [- 60.6, - 42.6] |
| Intent-to-Treat‡ | 27.3% (N=187) | 73.3% (N=206) | - 46.0 [- 54.8, - 37.2] |
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.
15. References
1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Tenth Edition. CLSI Document M07-A10, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania, 19087, USA 2015.
16. How is Aciphex supplied
ACIPHEX 20 mg is supplied as delayed-release light yellow enteric-coated tablets. The name and strength, in mg, (ACIPHEX 20) is imprinted on one side.
- Bottles of 30 (NDC 69784-243-30)
17. Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
| This Medication Guide has been approved by the U.S. Food and Drug Administration. | Revised: 03/2022 | ||
| MEDICATION GUIDE ACIPHEX® (a-se-feks) (rabeprazole sodium) delayed-release tablets |
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What is the most important information I should know about ACIPHEX?
You should take ACIPHEX exactly as prescribed, at the lowest dose possible and for the shortest time needed.
ACIPHEX can have other serious side effects. See "What are the possible side effects of ACIPHEX?" |
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| What is ACIPHEX?
ACIPHEX is a prescription medicine called a proton pump inhibitor (PPI). ACIPHEX reduces the amount of acid in your stomach. In adults, ACIPHEX is used for:
It is not known if ACIPHEX is safe and effective in children less than 12 years of age for other uses. ACIPHEX delayed-release tablets should not be used in children under 12 years of age. |
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Do not take ACIPHEX if you are:
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Before you take ACIPHEX, tell your doctor about all of your medical conditions, including if you:
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How should I take ACIPHEX?
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What are the possible side effects of ACIPHEX?
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| Stop taking ACIPHEX and call your doctor right away. These symptoms may be the first sign of a severe skin reaction. The most common side effects of ACIPHEX in adults include: pain, sore throat, gas, infection, and constipation. The most common side effects of ACIPHEX in adolescents 12 years of age and older include: headache, diarrhea, nausea, vomiting, and stomach-area (abdomen) pain. These are not all of the possible side effects of ACIPHEX. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. |
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| How should I store ACIPHEX?
Store ACIPHEX tablets in a dry place at room temperature between 68°F to 77°F (20°C to 25°C). Keep ACIPHEX and all medicines out of the reach of children. |
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| General Information about the safe and effective use of ACIPHEX.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ACIPHEX for a condition for which it was not prescribed. Do not give ACIPHEX to other people, even if they have the same symptoms that you have. It may harm them. You can ask your doctor or pharmacist for information about ACIPHEX that is written for health professionals. |
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| What are the ingredients in ACIPHEX?
Active ingredient: rabeprazole sodium Inactive ingredients: carnauba wax, crospovidone, diacetylated monoglycerides, ethylcellulose, hydroxypropyl cellulose, hypromellose phthalate, magnesium stearate, mannitol, sodium hydroxide, sodium stearyl fumarate, talc, and titanium dioxide. Iron oxide yellow is the coloring agent for the tablet coating. Iron oxide red is the ink pigment. Distributed by Woodward Pharma Services LLC, Wixom, MI 48393 All brand names are the trademarks of their respective owners. For more information, go to www.aciphex.com. |
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| ACIPHEX
rabeprazole sodium tablet, delayed release |
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| Labeler - Woodward Pharma Services LLC (080406260) |
