GENERIC NAME: omeprazole, omeprazole/sodium bicarbonate

BRAND NAME: Prilosec, Zegerid

DRUG CLASS AND MECHANISM: Omeprazole is in a class of drugs called proton pump
inhibitors (PPI) that block the production of acid by the stomach. Other drugs in the class include
lansoprazole (Prevacid), rabeprazole (Aciphex), pantoprazole (Protonix), and esomeprazole
(Nexium). Proton pump inhibitors are used for the treatment of conditions such as ulcers,
gastroesophageal reflux disease (GERD) and the Zollinger-Ellison syndrome, which are all
caused by stomach acid. Omeprazole, like other proton-pump inhibitors, blocks the enzyme in
the wall of the stomach that produces acid. By blocking the enzyme, the production of acid is
decreased, and this allows the stomach and esophagus to heal. Zegerid contains omeprazole and
an antacid (sodium bicarbonate). The FDA approved omeprazole in September 1989.

GENERIC AVAILABLE: Yes (Prilosec)

PRESCRIPTION: Yes; No (Prilosec OTC, Zegerid OTC)

PREPARATIONS: Capsules: 10, 20 and 40 mg. Tablets: 20 mg (Prilosec OTC). Powder for
oral suspension: 20 and 40 mg

STORAGE: Capsules should be stored at 15 to 30 C (59 to 86 F) and tablets at 20 to 25 C (68 to

77 F). They should be kept away from moisture and light.

PRESCRIBED FOR: Omeprazole is used for treating acid-induced inflammation and ulcers of
the stomach and duodenum; gastroesophageal reflux disease (GERD); erosive esophagitis,
heartburn; prevention of upper gastrointestinal bleeding in critically ill patients; and Zollinger-
Ellison Syndrome. It also is used in combination with antibiotics for eradicating H. pylori
infection of the stomach.

DOSING: For ulcers, GERD, erosive esophagitis and eradication of H. pylori the recommended
dose for adults is 20-40 mg daily. Ulcer healing usually occurs within 4-8 weeks.

H. pylori infections are treated for 10-28 days.

The usual dose for prevention of upper gastrointestinal bleeding in critically ill patients is 40 mg
daily for 14 days.

Prilosec OTC is used for treating heartburn for up to two weeks, and the usual dose is 20 mg
daily.

For the management of Zollinger-Ellison Syndrome the starting dose for adults is 60 mg daily,
and the dose is adjusted based on either the response of symptoms or the actual measurement of
acid production. Doses greater than 80 mg should be divided. Doses up to 120 mg three times a
day have been used in the treatment of Zollinger-Ellison Syndrome.
For maximal efficacy, omeprazole tablets should be taken before meals, swallowed whole and
should not be crushed, chewed or opened.

DRUG INTERACTIONS: Omeprazole potentially can increase the concentrations in blood of

diazepam (Valium), warfarin (Coumadin), and phenytoin (Dilantin) by decreasing the
elimination of these drugs by the liver.

The absorption of certain drugs may be affected by stomach acidity. Therefore, omeprazole as
well as other PPIs reduce the absorption and concentration in blood of ketoconazole (Nizoral)
and increase the absorption and concentration in blood of digoxin (Lanoxin). This may reduce
the effectiveness of ketoconazole or increase digoxin toxicity.

Through unknown mechanisms, omeprazole may increase blood levels of saquinavir and reduce
blood levels of nelfinavir and atazanavir, drugs that are used for treating patients with infection
caused by the human immunodeficiency virus (HIV). Accordingly, the dose of saquinavir may
need to be reduced to avoid toxicity, and the doses of nelfinavir and atazanavir may need to be
increased to maintain efficacy

Clopidogrel (Plavix) is converted to its active form by enzymes in the liver. Omeprazole reduces
the activity of these enzymes and potentially can reduce the activity of clopidogrel. Omeprazole
should not be used with clopidogrel.

Omeprazole increases the concentration of cilostazol (Pletal). The dose of cilostazol should be
reduced from 100 mg twice daily to 50 mg twice daily when given with omeprazole.

PREGNANCY: Use of omeprazole in pregnant women has not been adequately evaluated.
Omeprazole should be used during pregnancy only if the benefits justify the unknown risks.

NURSING MOTHERS: Omeprazole is excreted in breast milk and potentially could cause
adverse effects in the infant.

SIDE EFFECTS: Omeprazole like other PPIs is well-tolerated. The most common side effects
are diarrhea, nausea, vomiting, headaches, rash and dizziness. Nervousness, abnormal heartbeat,
muscle pain, weakness, leg cramps, and water retention occur infrequently.

Each packet of Zegerid powder for oral suspension contains 460 mg of sodium and each capsule
contains 304 mg of sodium. This should be taken into consideration in patients who need a
sodium restricted diet.

MECHAnisms:

Proton pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine

triphosphatase enzyme system (the H+/K+ ATPase, or, more common, gastric proton pump) of
the gastric parietal cell. The proton pump is the terminal stage in gastric acid secretion, being
directly responsible for secreting H+ ions into the gastric lumen, making it an ideal target for
inhibiting acid secretion. ("Irreversibility" refers to the effect on a single copy of the enzyme; the
effect on the overall human digestive system is reversible, as the enzymes are naturally destroyed
and replaced with new copies.)

Targeting the terminal step in acid production, as well as the irreversible nature of the inhibition,
results in a class of drugs that are significantly more effective than H2 antagonists and reduce
gastric acid secretion by up to 99%.

The lack of the acid in the stomach will aid in the healing of duodenal ulcers, and reduces the
pain from indigestion and heartburn, which can be exacerbated by stomach acid. However, lack
of stomach acid is also called hypochlorhydria, the lack of sufficient hydrochloric acid, or HCl.
Hydrochloric acid is required for the digestion of proteins and for the absorption of nutrients,
particularly of vitamin B12 and of calcium.

The proton pump inhibitors are given in an inactive form. The inactive form is neutrally charged
(lipophilic) and readily crosses cell membranes into intracellular compartments (like the parietal
cell canaliculus) that have acidic environments. In an acid environment, the inactive drug is
protonated and rearranges into its active form. As described above, the active form will
covalently and irreversibly bind to the gastric proton pump, deactivating it.

[edit] Potassium-competitive acid blockers (P-CABs)

Potassium-competitive inhibitors are experimental drugs that reversibly block the potassium
binding site of the proton pump. Soraprazan and revaprazan block H+ secretion much more
quickly than classical PPIs (within a half-hour).[5] The development of soraprazan, however, has
been discontinued in 2007.[6]

[edit] Pharmacokinetics

In general, the absorption of proton pump inhibitors is unaffected by co-administration with

food. The rate of omeprazole absorption, however, is decreased by concomitant food intake. In
addition, the absorption of lansoprazole and esomeprazole is decreased and delayed by food. It
has been reported that these pharmacokinetic effects, however, have no significant impact on
efficacy.[7][8]

The elimination half-life of proton pump inhibitors ranges from 0.5–2 hours, however the effect
of a single dose on acid secretion usually persists up to 2–3 days. This is because of
accumulation of the drug in parietal cell canaliculi and the irreversible nature of proton pump
inhibition.

Adverse effects

In general, proton pump inhibitors are well tolerated, and the incidence of short-term adverse
effects is relatively uncommon. The range and occurrence of adverse effects are similar for all of
the proton pump inhibitors, though they have been reported more frequently with omeprazole.
This may be due to its longer availability and, hence, clinical experience.
Common adverse effects include: headache, nausea, diarrhea, abdominal pain, fatigue, and
dizziness.[9]

Infrequent adverse effects include rash, itch, flatulence, constipation, anxiety, and depression.
Decreased vitamin B12 absorption may occur with long-term use.[9] Rarely PPI cause
‘idiosyncratic’ reactions such as erythema multiforme, pancreatitis, Stevens Johnson syndrome,
and acute interstitial nephritis.[10]

It has been observed that gastric acid suppression, using H2-receptor antagonists and proton
pump inhibitors, is associated with an increased risk of community-acquired pneumonia. It is
suspected that acid suppression results in insufficient elimination of pathogenic organisms.
Therefore, it has been suggested that patients at higher risk of pneumonia should be prescribed
proton pump inhibitors only at lower doses and only when necessary.[11]

PPIs have been shown to raise risk of Clostridium difficile infection by 1.7 with once daily use
and 2.4 with more than once daily use.[12] The risk can be minimized by judicious short term
prescriptions.[13]

Long-term use of proton pump inhibitors has been less studied. But, in a study of 135,000 people
50 or older, those taking high doses of PPIs for longer than one year have been found to be 2.6
times more likely to break a hip. Those taking smaller doses for 1 to 4 years were 1.2 to 1.6
times more likely to break a hip. The risk of a fracture increased with the length of time taking
PPIs.[14][15][16] Theories as to the cause of the increase are the possibility that the reduction of
stomach acid reduces the amount of calcium dissolved in the stomach or that PPIs may interfere
with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts.
[17]
Also, the reduction of vitamin B12 (by raising homocysteine) may increase bone fragility, an
effect that may be offset by the consumption, or by the co-packaging, of about 100 mcg of B12
with the PPI.

A recent study has also suggested that proton pump inhibitors significantly decreased the effect
of clopidogrel on platelets as tested by VASP phosphorylation. The clinical impact of these
results must be assessed by further investigations, but a PPI treatment should not be added to the
antiplatelet dual therapy without formal indication.[18]

A 2009 report in Gastroenterology suggests that PPIs may cause dependency by increasing
gastric symptoms if they are discontinued.[19]

The FDA is revising both the prescription and the over-the-counter (OTC) labels for PPIs to
include the possible increased risk of fractures.

This new information is based upon FDA review of several long-term studies that reported an
increased risk of fractures of the hip, wrist, and spine with PPI use. Some studies found a greater
risk for these fractures from higher doses of PPI or use for one year or more. Most studies
evaluated individuals aged 50 or older and the increased risk of fractures was primarily in this
group.