o-MEP-ra-zole

Therapeutic Classification: antiulcer agents

Pharmacologic Classification: proton pump inhibitors

• GERD/maintenance of healing in erosive esophagitis.
• Duodenal ulcers (with or without anti-infectives for Helicobacter pylori).
• Short-term treatment of active benign gastric ulcer.
• Pathologic hypersecretory conditions, including Zollinger-Ellison syndrome.
• Reduction of risk of GI bleeding in critically ill patients.

OTC:

• Heartburn occurring twice/wk.

• Binds to an enzyme on gastric parietal cells 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 gastroesophageal reflux.
• Healing of duodenal ulcers.

Absorption: Rapidly absorbed following oral administration; immediate release formulation contains bicarbonate to prevent acid degradation.

Distribution: Good distribution into gastric parietal cells.

Protein Binding: 95%.

Metabolism/Excretion: Mostly metabolized by the liver via the CYP2C19 isoenzyme, and to a lesser extent by the CYP3A4 isoenzyme; the CYP2C19 isoenzyme exhibits genetic polymorphism (15–20% of Asian patients and 3–5% of Caucasian and Black patients may be poor metabolizers and may have significantly ↑ omeprazole concentrations and an ↑ risk of adverse effects); inactive metabolites are excreted in urine (77%) and feces.

Half-life: 0.5–1 hr (↑ in liver disease to 3 hr).

(antisecretory effects)

Contraindicated in:

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

Use Cautiously in:

• Hepatic impairment (dose ↓ 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
• Lactation: Safety not established in breastfeeding
• Pedi: Children <1 mo (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).

CV: chest pain.

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

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, flatulence, fundic gland polyps, nausea, vomiting.

GU: acute tubulointerstitial nephritis.

MS: bone fracture.

Neuro: dizziness, drowsiness, fatigue, headache, weakness.
Misc: (INCLUDING ANAPHYLAXIS, ANGIOEDEMA, OR TUBULOINTERSTITIAL NEPHRITIS)HYPERSENSITIVITY REACTIONS , systemic lupus erythematosus, vitamin B₁₂ deficiency.

Drug-Drug:

• May significantly ↓ levels and effectiveness of rilpivirine; concurrent use contraindicated.
• May ↑ levels and risk of toxicity of antifungal agents, cilostazol, citalopram, diazepam, triazolam, cyclosporine, phenytoin, tacrolimus, and warfarin; consider ↓ dose of cilostazol from 100 mg twice daily to 50 mg twice daily.
• May ↓ absorption of drugs requiring acid pH, including ketoconazole, itraconazole, iron salts, dasatinib, erlotinib, nilotinib, atazanavir, nelfinavir, and mycophenolate mofetil; avoid concurrent use with atazanavir and nelfinavir.
• May ↑ levels of digoxin and methotrexate.
• Voriconazole may ↑ levels.
• May ↓ the antiplatelet effects of clopidogrel; avoid concurrent use.
• Rifampin may ↓ levels and may ↓ response; avoid concurrent use.
• Hypomagnesemia and hypokalemia ↑ risk of digoxin toxicity.

Drug-Natural Products:

• St. John's wort may ↓ levels and may ↓ response; avoid concurrent use.

• PO (Adults): GERD/erosive esophagitis and maintenance of healing of erosive esophagitis: 20 mg once daily. Duodenal ulcers associated with H. pylori: 40 mg once daily in the morning with clarithromycin for 2 wk, then 20 mg once daily for 2 wk or 20 mg twice daily with clarithromycin 500 mg twice daily and amoxicillin 1000 mg twice daily for 10 days (if ulcer is present at beginning of therapy, continue omeprazole 20 mg daily for 18 more days); has also been used with clarithromycin and metronidazole. Gastric ulcer: 40 mg once daily for 4–6 wk. Reduction of the risk of GI bleeding in critically ill patients: 40 mg initially, then another 40 mg 6–8 hr later, followed by 40 mg once daily for up to 14 days. Gastric hypersecretory conditions: 60 mg once daily initially; may be increased up to 120 mg 3 times daily (doses >80 mg/day should be given in divided doses); OTC: 20 mg once daily for up to 14 days.
• PO (Children 1–16 yr and 20 kg): GERD/erosive esophagitis: 20 mg once daily for 4–8 wk.
• PO (Children 1–16 yr and 10–19 kg): GERD/erosive esophagitis: 10 mg once daily for 4–8 wk.
• PO (Children 1–16 yr and 5–9 kg): GERD/erosive esophagitis: 5 mg once daily for 4–8 wk.
• PO (Children 1 mo–<1 yr and 10 kg): Erosive esophagitis: 10 mg once daily for up to 6 wk.
• PO (Children 1 mo–<1 yr and 5–9 kg): Erosive esophagitis: 5 mg once daily for up to 6 wk.
• PO (Children 1 mo–<1 yr and 3–4 kg): Erosive esophagitis: 2.5 mg once daily for up to 6 wk.

(Generic available)

• Delayed-release tablets: 10 mg; 20 mg^OTC;
• Delayed-release capsules: 10 mg; 20 mg; 40 mg;
• Delayed-release powder for oral suspension (peach-mint flavor): 2.5 mg/packet; 10 mg/packet;
• In combination with: metronidazole and clarithromycin in a compliance package (Losec 1-2-3 M); amoxicillin and clarithromycin in a compliance package (Losec 1-2-3-A) (both in Canada only); amoxicillin and rifabutin (Talicia); sodium bicarbonate (Konvomep, Zegerid [OTC]). See Appendix [not included in this PDA edition].

• Assess patient 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 CBC with differential periodically during therapy.
  • May cause ↑ AST, ALT, alkaline phosphatase, and bilirubin.
  • May cause serum gastrin concentrations to ↑ during first 1–2 wk of therapy. Levels return to normal after discontinuation of omeprazole.
  • Monitor INR and prothrombin time in patients taking warfarin.
  • May cause hypomagnesemia. Monitor serum magnesium prior to and periodically during therapy.
  • May cause false positive results in diagnostic investigations for neuroendocrine tumors due to ↑ serum chromogranin A (CgA) levels secondary to drug-induced ↓ gastric acidity. Temporarily stop omeprazole at least 14 days before assessing CgA levels and consider repeating test if initial CgA levels are high.

• Do not confuse Prilosec with Prozac or Pristiq. Do not confuse omeprazole with fomepizole.
• PO: Administer doses before meals, preferably in the morning. DNC: Swallow capsules and tablets whole; do not crush or chew. Capsules may be opened and sprinkled on cool applesauce, entire mixture should be ingested immediately and followed by a drink of water. Do not store for future use.
  • Powder for oral suspension: Administer on empty stomach, at least 1 hr before a meal. Empty contents of 2.5-mg packet into 5 mL of water or contents of 10 mg packet into 15 mL of water. Stir. Leave 2–3 min to thicken. Stir and drink within 30 min. If material remains after drinking, add more water, stir and drink immediately. For patients with nasogastric or enteral feeding, suspend feeding for 3 hr before and 1 hr after administration. Empty packet contents into a small cup containing 5 mL of water for 2.5-mg dose or 15 mL water for 10-mg dose using a catheter tipped syringe. Do not use other liquids or foods. Immediately shake syringe and leave 2–3 min to thicken. Administer within 30 min. Refill the syringe with an equal amount of water. Shake and flush remaining contents from nasogastric or gastric tube into stomach.
  • May be administered concurrently with antacids.

• 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.
• Instruct patient to notify healthcare professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
• Advise patient to avoid alcohol, products containing aspirin or NSAIDs, and foods that may cause an increase in GI irritation.
• 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 onset of black, tarry stools; diarrhea; abdominal pain; 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 healthcare professional if pregnancy is planned or suspected, or if breastfeeding.

• Decrease in abdominal pain or prevention of gastric irritation and bleeding. Healing of duodenal ulcers can be seen on x-ray examination or endoscopy.
• Decrease in symptoms of GERD and erosive esophagitis. Therapy is continued for 4–8 wk after initial episode.

PriLOSEC, PriLOSEC OTC

Losec