ra-BEP-ra-zole

Therapeutic Classification: antiulcer agents

Pharmacologic Classification: proton pump inhibitors

• Gastroesophageal reflux disease (GERD).
• Duodenal ulcers (including combination therapy with clarithromycin and amoxicillin to eradicate Helicobacter pylori and prevent recurrence).
• Pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

• Binds to an enzyme in the presence of acidic gastric pH, preventing the final transport of hydrogen ions into the gastric lumen.

• Diminished accumulation of acid in the gastric lumen, with lessened acid reflux.
• Healing of duodenal ulcers and esophagitis.
• Decreased acid secretion in hypersecretory conditions.

Absorption: Delayed-release tablet is designed to allow rabeprazole, which is not stable in gastric acid, to pass through the stomach intact. Subsequently 52% is absorbed after oral administration.

Distribution: Unknown.

Protein Binding: 96.3%.

Metabolism/Excretion: Mostly metabolized by the CYP3A4 and CYP2C19 isoenzymes in the liver; (the CYP2C19 enzyme system exhibits genetic polymorphism; 15–20% of Asian patients and 3–5% of Caucasian and Black patients may be poor metabolizers and may have significantly ↑ rabeprazole concentrations and an ↑ risk of adverse effects); 10% excreted in feces; remainder excreted in urine as inactive metabolites.

Half-life: 1–2 hr.

(acid suppression)

†Suppression continues to increase over the first wk of therapy.

Contraindicated in:

• Hypersensitivity to rabeprazole or related drugs (benzimidazoles)
• Concurrent use of rilpivirine.

Use Cautiously in:

• Severe hepatic impairment (dose reduction may be necessary)
• Patients using high doses for >1 yr (↑ risk of hip, wrist, or spine fractures and fundic gland polyps)
• Patients using therapy for >3 yr (↑ risk of vitamin B₁₂ deficiency)
• Pre-existing risk of hypocalcemia
• OB: Safety not established in pregnancy
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Pedi: Children <12 yr (safety and effectiveness not established)
• Geri: Appears on Beers list. ↑ risk of Clostridioides difficile infection, pneumonia, GI malignancies, bone loss, and fractures in older adults. Avoid scheduled use for >8 wk in older adults unless for high-risk patients (e.g., oral corticosteroid or chronic NSAID use) or patients with erosive esophagitis, Barrett's esophagitis, pathological hypersecretory condition, or demonstrated need for maintenance therapy (e.g., failure of H₂ antagonist).

Derm: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS (AGEP), cutaneous lupus erythematosus, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), photosensitivity, rash, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN).

F and E: hypocalcemia (especially if treatment duration 3 mo), hypokalemia (especially if treatment duration 3 mo), hypomagnesemia (especially if treatment duration 3 mo).

GI: abdominal pain, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), constipation, diarrhea, fundic gland polyps, nausea.

GU: acute tubulointerstitial nephritis.

MS: bone fracture, neck pain.

Neuro: dizziness, headache, malaise.
Misc: chills, fever, (INCLUDING ANAPHYLAXIS, ANGIOEDEMA, OR TUBULOINTERSTITIAL NEPHRITIS)HYPERSENSITIVITY REACTIONS , systemic lupus erythematosus, vitamin B₁₂ deficiency.

Drug-Drug:

• May ↓ absorption of drugs requiring acid pH, including ketoconazole, itraconazole, atazanavir, iron salts, erlotinib, dasatinib, nelfinavir, nilotinib, rilpivirine, and mycophenolate mofetil; concurrent use with rilpivirine contraindicated; avoid concurrent use with nelfinavir.
• May ↑ levels of digoxin, methotrexate, and tacrolimus.
• Hypomagnesemia and hypokalemia ↑ risk of digoxin toxicity.
• May ↑ the risk of bleeding with warfarin (monitor INR).

Gastroesophageal Reflux Disease

• PO (Adults): Healing of erosive or ulcerative GERD: 20 mg once daily for 4–8 wk; Maintenance of healing of erosive or ulcerative GERD: 20 mg once daily; Symptomatic GERD: 20 mg once daily for 4 wk (additional 4 wk may be considered for nonresponders).
• PO (Children 12 yr): Short-term treatment of symptomatic GERD: 20 mg once daily for up to 8 wk.
• PO (Children 1–11 yr): 15 kg: 10 mg once daily for up to 12 wk (given as sprinkle); <15 kg: 5 mg once daily for up to 12 wk (given as sprinkle); may ↑ up to 10 mg once daily if inadequate response.

Duodenal Ulcers

• PO (Adults): Healing of duodenal ulcers: 20 mg once daily for up to 4 wk.

H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence (Triple Therapy)

• PO (Adults): 20 mg twice daily for 7 days, with amoxicillin 1000 mg twice daily for 7 days and clarithromycin 500 mg twice daily for 7 days.

Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome

• PO (Adults): 60 mg once daily initially; may be adjusted as needed and continued as necessary; doses up to 100 mg daily or 60 mg twice daily have been used.

(Generic available)

• Delayed-release capsules (sprinkle): 10 mg;
• Delayed-release tablets: 10 mg; 20 mg;

• Assess routinely for epigastric or abdominal pain and frank or occult blood in the stool, emesis, or gastric aspirate.
• Monitor bowel function. Report diarrhea, abdominal cramping, fever, and bloody stools to health care professional promptly as a sign of CDAD. May begin up to several wk following cessation of therapy.
• Monitor for rash or other cutaneous reactions. May cause SJS, TEN, DRESS, and AGEP. Discontinue rabeprazole at the first sign of severe cutaneous adverse reactions.

• Monitor CBC with differential periodically during therapy.
  • May cause hypomagnesemia. Monitor serum magnesium prior to and periodically during therapy.

• High Alert:Do not confuse rabeprazole with aripiprazole. Do not confuse Aciphex with Accupril or Aricept.
• PO: Administer without regard to food, preferably in the morning. DNC: Tablets should be swallowed whole; do not break, crush, or chew.
  • For treatment of duodenal ulcers, take after a meal.
  • For Helicobacter pylori eradication, take tablets with food.
  • Capsules may be opened and sprinkled on a small amount of soft food (apple sauce, fruit, or vegetable-based baby food, yogurt) or empty contents into small amount of liquid (infant formula, apple juice, pediatric electrolyte solution). Food or liquid should be at or below room temperature. Whole dose should be taken within 15 min of being sprinkled. Granules should not be chewed or crushed. Dose should be taken 30 min before a meal. Do not store mixture for future use.

• Instruct patient to take medication as directed for the full course of therapy, even if feeling better. Take missed doses as soon as remembered but not if almost time for next dose. Do not double doses.
• May cause occasional drowsiness or dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Advise patient to avoid alcohol, products containing aspirin or NSAIDs, and foods that may cause an increase in GI irritation.
• Caution patients to wear sunscreen and protective clothing to prevent photosensitivity reactions.
• Advise patient to report onset of black, tarry stools; diarrhea; abdominal pain; or persistent headache to health care professional promptly.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Instruct patient to notify health care professional of onset of black, tarry stools; diarrhea; abdominal pain; or persistent headache or if fever and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

• Decrease in abdominal pain or prevention of gastric irritation and bleeding.
• Decrease in symptoms of GERD.
• Decreased acid secretion in hypersecretory conditions.

Aciphex, Aciphex Sprinkle

Pariet