ACIPHEX®(rabeprazole sodium)

ACIPHEX®(rabeprazole sodium)

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ACIPHEX®(rabeprazole sodium)

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.

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.

Indications and usage

ACIPHEX delayed-release tablets is a proton pump inhibitor (PPI) indicated in adults for:

  • Healing of Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD)
  • Maintenance of Healing of Erosive or Ulcerative GERD
  • Treatment of Symptomatic GERD
  • Healing of Duodenal Ulcers
  • Helicobacter pylori Eradication to Reduce Risk of Duodenal Ulcer Recurrence
  • Treatment of Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome

In adolescent patients 12 years of age and older for:

  • Short-term Treatment of Symptomatic GERD

Mechanism of Action

Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole protonpump 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.

Dosage and administration

IndicationRecommended Dosage
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 months20 mg once daily*
Symptomatic GERD in Adults 20 mg once daily for 4 weeks20 mg once daily for 4 weeks
Healing of Duodenal Ulcers 20 mg once daily after morning meal for up to 4 weeks20 mg once daily after morning meal for up to 4 weeks
Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence ACIPHEX 20 mg Amoxicillin 1000 mg daily Clarithromycin 500 mgAll three medications should be taken twice with morning and evening meals for 7 days
Pathological Hypersecretory Conditions, Including Zollinger-Ellison SyndromeStarting dose 60 mg once daily then adjust to patient needs
Symptomatic GERD in Adolescents 12 Years of Age and Older20 mg once daily for 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.

Administration Instructions:

  • Swallow ACIPHEX delayed-release tablets whole. Do not chew, crush or split the tablets.
  • For the treatment of duodenal ulcers take ACIPHEX delayedrelease tablets after a meal.
  • For Helicobacter pylori eradication take ACIPHEX delayedrelease tablets with food.
  • For all other indications ACIPHEX delayed-release tablets can be taken with or without food.

Contraindications

  • Patients with a history of hypersensitivity to rabeprazole
  • PPIs, including ACIPHEX delayed-release tablets, are contraindicated in patients receiving rilpivirine-containing products

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
  • Use with Warfarin: Monitor for increases in INR and prothrombin time
  • Acute Tubulointerstitial Nephritis: Discontinue treatment and evaluate patients
  • Clostridium difficile-Associated Diarrhea: PPI therapy may be associated with increased risk of
  • 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
  • Cutaneous and Systemic Lupus Erythematosus: Mostly cutaneous, new onset or exacerbation of existing disease; discontinue ACIPHEX and refer to specialist for evaluation
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  • Cyanocobalamin (Vitamin B-12) Deficiency: Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin
  • Hypomagnesemia: Reported rarely with prolonged treatment with PPIs
  • 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
  • Fundic Gland Polyps: Risk increases with long-term use, especially beyond one year. Use the shortest duration of therapy

Adverse reactions

Most common adverse reactions in adults (>2%) are pain, pharyngitis, flatulence, infection, and constipation

Most common adverse reactions in adolescents (≥2%) are headache, diarrhea, nausea, vomiting, and abdominal pain

Drug interactions

Antiretrovirals: The effect of PPI on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known.

  • Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with rabeprazole may reduce antiviral effect and promote the development of drug resistance.
  • Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with rabeprazole may increase toxicity.
  • There are other antiretroviral drugs which do not result in clinically relevant interactions with rabeprazole.

Warfarin: 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

Methotrexate: 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

Digoxin: Potential for increased exposure of digoxin

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole, itraconazole): Rabeprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity.

Combination Therapy with Clarithromycin and Amoxicillin: 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

Tacrolimus: Potentially increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19.

Interactions with Investigations of Neuroendocrine Tumors: Serum chromogranin A (CgA) levels increase secondary to PPIinduced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors.

Interaction with Secretin Stimulation Test: Hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma.

False Positive Urine Tests for THC: There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs.

Use in specific populations

Pregnancy: There are no available human data on ACIPHEX use in pregnant women to inform the drug associated risk. The background risk of major birth defects and miscarriage for the indicated populations are unknown.

Lactation: Lactation studies have not been conducted to assess the presence of rabeprazole in human milk, the effects of rabeprazole on the breastfed infant, or the effects of rabeprazole on milk production. Rabeprazole is present in rat milk. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for ACIPHEX and any potential adverse effects on the breastfed infant from ACIPHEX or from the underlying maternal condition.

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.

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.

Storage

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Protect from moisture.

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