Omeprazole (
INN) is a
proton pump inhibitor used in the treatment of
dyspepsia,
peptic ulcer disease (PUD),
gastroesophageal reflux disease (GORD/GERD) and
Zollinger-Ellison syndrome. It was first marketed by
AstraZeneca as the
magnesium salt omeprazole magnesium under the trade names
Losec and
Prilosec, and is now also available from
generic manufacturers under various trade names. Omeprazole is one of the most widely prescribed drugs internationally and is available
over the counter in some countries.
Pharmacology
Omeprazole is a
racemate (containing a tricoordinated sulfur atom in a pyramidal structure and therefore can exist in equal amounts of both the S and R
enantiomers). In the acidic conditions of the stomach, both are converted to achiral products, which reacts with a cysteine group in
H+/K+ ATPase, thereby destroying the ability of the
parietal cells to produce
gastric acid.
Facing the loss of patent protection and competition from generic drug manufacturers, AstraZeneca developed and heavily marketed esomeprazole (Nexium) as a replacement. Esomeprazole is the S-enantiomer in the pure form.
According to AstraZeneca, omeprazole undergoes a chiral shift in vivo which converts the inactive R-enantiomer to the active S-enantiomer doubling the concentration of the active form. This chiral shift is accomplished by the CYP2C19 isozyme of cytochrome P450, which is not found equally in all human populations. Those who do not metabolize the drug effectively are called "poor metabolizers." The approximate proportion of the poor metabolizer phenotype in different populations is as follows:
- Caucasians 10%
- Asian 20%
- South Pacific Islands 70%
In theory, by using pure esomeprazole the effect on the proton pump will be equal in all patients, eliminating the "poor metabolizer effect".
Name change
In 1990, at the request of the
United States Food and Drug Administration (FDA), the brand name
Losec was changed to
Prilosec to avoid confusion with the
diuretic Lasix (
furosemide). Unfortunately, the new name has led to confusion between omeprazole (
Prilosec) and
fluoxetine (
Prozac), an
antidepressant.
Clinical use
Use in Helicobacter pylori eradication
Omeprazole is combined with the antibiotics
clarithromycin and
amoxicillin (or
metronidazole in penicillin-hypersensitive patients) in the 7-14 day eradication triple therapy for
Helicobacter pylori. Infection by
H. pylori is the causative factor in the majority of
peptic and
duodenal ulcers.
Dosage forms
Omeprazole is available as tablets and capsules (containing omeprazole or omeprazole magnesium) in strengths of 10 mg, 20 mg, and in some markets 40 mg; and as a powder (omeprazole sodium) for intravenous injection. Most oral omeprazole preparations are enteric-coated, due to the rapid degradation of the drug in the acidic conditions of the stomach. This is most commonly achieved by formulating enteric-coated granules within capsules, enteric-coated tablets, and the multiple-unit pellet system.
It is also available for use in injectable form (I.V.) in Europe, but not in the U.S.
The injection pack is a combination pack consisting of a vial and a separate ampule of reconstituting solution. Each 10 ml clear glass vial contains a white to off-white lyophilised powder consisting of omeprazole sodium 42.6 mg equivalent to 40 mg of omeprazole.
Losec is manufactured by AstraZeneca, Södertälje, Sweden.
Multiple unit pellet system
Omeprazole tablets manufactured by AstraZeneca (notably Losec/Prilosec) are formulated as a "multiple unit pellet system" (MUPS). Essentially, the
tablet consists of extremely small enteric-coated granules (pellets) of the omeprazole formulation inside an outer shell. When the tablet is immersed in an aqueous solution, as happens when the tablet reaches the stomach, water enters the tablet by
osmosis. The contents swell from water absorption causing the shell to burst, releasing the enteric-coated granules. For most patients, the multiple-unit pellet system is of no advantage over conventional enteric-coated preparations. Patients for which the formulation is of benefit include those requiring
nasogastric tube feeding and those with difficulty swallowing (
dysphagia).
The granules are manufactured in a fluid air bed system. Sugar spheres in suspension are sequentially sprayed with aqueous suspensions of omeprazole, a protective layer, an enteric coating and an outer layer to reduce granule aggregation. The granules are mixed with other excipients and compressed into tablets. Finally, the tablets are film-coated to improve the stability and appearance of the preparation.
Immediate release formulation
In June 2004 the FDA approved an immediate release preparation of
omeprazole/sodium bicarbonate that does not require an enteric coating. This preparation employs
sodium bicarbonate as a buffer to protect omeprazole from gastric acid degradation. This allows for the production of chewable tablets. This combination preparation is marketed in the United States by
Santarus under the trade name
Zegerid. Zegerid is marketed as capsules, chewable tablets, and powder for oral suspension. Zegerid is most useful for those patients who suffer from nocturnal acid breakthrough (NAB) or those patients who desire immediate relief.
In India it is marketed by Dr Reddy's Labs as powder formulation with the brand name-
OMEZ-INSTA. It is reported to have additional benefits with patients suffering from Alcoholic Gastritis and Life-Style associated Gastritis.
Side effects
As with all proton pump inhibitors, omeprazole is generally well tolerated. Some of the most frequent
side effects of omeprazole (experienced by over 1% of those taking the drug) are
headache,
diarrhea, abdominal pain,
nausea and
dizziness, although in
clinical trials the incidence of these effects with omeprazole was mostly comparable to that found with
placebo.
Proton pump inhibitors may be associated with a greater risk of hip fractures and clostridium difficile diarrhoea.
Absorption and distribution
The absorption of omeprazole takes place in the small intestine and is usually completed within 3-6 hours. The systemic
bioavailability of omeprazole after repeated dose is about 60%. Concomitant intake of food has no influence on the bioavailability. Plasma protein binding is about 95%.
Metabolism and excretion
Omeprazole is completely metabolised by the
cytochrome P450 system, mainly in the liver. Identified metabolites are the
sulfone, the
sulfide and hydroxy-omeprazole, which exert no significant effect on the acid secretion. About 80% of an orally given dose is excreted as metabolites in the urine and the remainder is found in the feces, primarily originating from bile secretion.
Brand names
- OMEZ (Dr Reddy's Laboratories Ltd India)- FGP
- Gasec (Mepha)
- RISEK (GETZ PHARMA)
- Zegerid
- Prilosec, Losec, Prilosec OTC, Omez
- Antra in Italy
- Nexium (esomeprazole, a S-enantiomer of omeprazole)
- Ozid (in Indonesia)
- * Omepradex (Dexcel, Israel)
- ONIZ 20 (Nepal, Nepal Pharmaceuticals)
- Ortanol (Lek Polska Sp. z o.o.)
- Procepin (OMEPRAZOLE in Singapore)
- Odasole Caps/ Inj. (Greece & Sudan)
- Omeprol (Serbia)
- Omep (Sandoz)
- Ompic (Pharma Corp Inc, India)
- Ocid (India)
- Miracid (Thailand)
- Omepron (Philippines)
- Ucetal (SERRAL, Mexico)
References
Ocid.Zydus Cadila.
Omezol (Bosch Pharmaceuticals - Pakistan )
External links
