AcipHex: Package Insert and Label Information

ACIPHEX- rabeprazole sodium tablet, delayed release
Eisai Inc.

1 INDICATIONS AND USAGE

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].

1.6 Treatment of Pathological Hypersecretory Conditio ns, Including Zollinger-Ellison Syndrome in Adults

ACIPHEX delayed-release tablets are indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

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

ACIPHEX delayed-release tablets are indicated for the treatment of symptomatic GERD in adolescents 12 years of age and above for up to 8 weeks.

2 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 mgAmoxicillin 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 dosesDosages 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 Instruction s

  • 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.

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 interstitial nephritis, and urticaria [see 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 G astric M alignancy

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 W arfarin

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 Interstitial Nephritis

Acute interstitial nephritis has been observed in patients taking PPIs including ACIPHEX. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue ACIPHEX if acute interstitial nephritis develops [ see Contraindications (4)] .

5. 4 Clostridium difficile - A ssociated D iarrhea

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 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.

5.7 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.

5.8 Hypomagnesemia

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. 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), healthcare professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2)].

5. 9 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 .10 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

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

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