O
meprazole is a proton-pumpinhibitor labeled for treatingand preventing the recur-rence of gastric ulcers in horses andfoals (at least 4 weeks of age). It isused short-term in humans for a va-riety of gastrointestinal problems.
PHARMACOLOGY
After oral administration, omepra-zole blocks the final step in gastric-acid production. Hydrogen/potassium(H
+
/K
+
) ATPase, a membrane-span-ning enzyme located on the secretory surface of the parietal cells in thestomach, moves protons (hydrogenions) across the parietal-cell mem-brane in exchange for potassiumions. Once the protons enter thestomach lumen, hydrochloric acid isformed. At a neutral pH, omeprazoleis a lipophilic weak base; this neutralmolecule easily passes from the circu-lation to the secretory canaliculus of active parietal cells. In the parietalcells, omeprazole is exposed to acidicconditions; at this point, the drug isno longer lipophilic but rather be-comes protonated and trapped. Inthis environment, omeprazole is con-verted to a sulfonamide metaboliteand covalently binds to the externalsurface of the H
+
/K
+
ATPase enzyme,blocking its activity.
1–4
Omeprazole is readily absorbed af-ter oral administration. Because itdegrades rapidly in an acidic envi-ronment, human formulations areenteric coated to allow absorption tooccur in the more neutral environ-ment of the small intestine. The vet-erinary product is not coated. Peak plasma concentration occurs 0.5 to3.5 hours after oral administration inhumans
3
and approximately 4 hoursafter administration in horses.
5
It isrecommended that human-labeledomeprazole be given before eating toblock acid secretion
3
; however, bio-availability and efficacy do not appearto be significantly altered by food.
6
Bioavailability of the veterinary-la-beled product has been documentedto decrease by 67% when adminis-tered with food, but this is not be-lieved to significantly affect thedrug’s efficacy.
5,7
Bioavailability in-creases slightly with repeated admin-istration,
3
possibly because of in-creased gastric pH. As mentioned,omeprazole requires a neutral envi-ronment to be absorbed. Because itsmechanism blocks proton secretion,the stomach environment becomes
Small Animal/Exotics
Compendium
August 2000
less acidic, possibly allowing someabsorption to occur before the drugreaches the small intestine.
8
Despite its relatively short half-life,omeprazole has a long duration of ac-tion. Although the reported half-life indogs is approximately 1 hour,
8,9
a sin-gle dose has been shown to affect acidsecretion from 24 hours
9
to 4 days
10
asa result of accumulation in the parietalcells and covalent binding to theH
+
/K
+
ATPase enzymes. Because of itsprolonged duration of action, omepra-zole is administered once daily. Indogs and horses, peak acid suppressionoccurs after four to five doses.
5,8
In humans, omeprazole is metabo-lized by the cytochrome P-450 en-zyme system to inactive metabolites;80% of metabolites are recovered inurine, with the remainder recoveredin feces.
1
Dose adjustments for he-patic or renal insufficiency are not re-quired in humans.
1,2
Information re-garding the equine product does notspecify whether dose adjustment isnecessary for these conditions inhorses. Whether dose adjustmentsare warranted in dogs is unknown.
2
INDICATIONS
In humans, omeprazole is indicat-
Leigh Liles Foushee, PharmD, RPhCommunity Pharmacy ResidentCentral Pharmacy andCompounding CenterCampbell UniversityBuies Creek, NC
PHARM PROFILE
OMEPRAZOLE
Pharm Profile
introduces drugs that are new to the veterinary market as well as new indications for existing drugs. If you would like
Pharm Profile
to cover a particular agent, please contact column editor Gigi Davidson, BS, RPh, North Carolina State University,4700 Hillsborough Street, Raleigh, NC 27606; phone 919-821-9500 • fax 919-829-4225 • email gigi_davidson@ncsu.edu.
Compendium
August 2000Small Animal/Exotics
CAUTIONS
During the initial toxicity studiesof omeprazole, rats commonly devel-oped gastric carcinoid tumors andhyperplasia of the enterochromaffin-like cells after long-term administra-tion.
1,2,8,9
Thus the FDA restrictedthe use of omeprazole in humans toshort-term therapy (no longer than 8 weeks) except in patients with Zoll-inger–Ellison syndrome, in whichthe benefit exceeds the risk. Researchhas indicated a relationship betweenomeprazole-induced hypergastrine-mia and hyperplasia of the ente-rochromaffin-like cells.
1,2,8,9
Similareffects have been noted with raniti-dine, suggesting that perhaps thisrisk is not directly associated withthe drug but rather with long-termsuppression of gastric acid.
1,2
Similar concerns may exist fordogs and horses, although no docu-mented cases could be found. As inhumans, omeprazole use in dogs isbelieved to be safe for up to 4 weeks.Treating for periods up to 8 weeksshould be done with caution.
8
Thesafety of using omeprazole paste (2mg/kg/day) in horses beyond 91 dayshas not been determined.
7
Contraindications
Omeprazole is contraindicated inpatients with a known hypersensitivi-ty to it or any component in its for-mulation. Because omeprazole is abenzimidazole that causes blood dys-crasia in humans and tumors in labo-ratory animals, it should not be usedin animals intended for food produc-tion.
Adverse Reactions
Omeprazole is well tolerated inhumans (Table I).
3
Life-threateningor fatal pancreatitis, liver necrosis orfailure, pancytopenia, and agranulo-cytosis have occurred in less than 1%of patients. Use of omeprazole in dogsand horses has not produced clinical,hematologic, or biochemical abnor-malities.
2,14
The only reported com-plication associated with omeprazolein horses was a spontaneously resolv-ingurticaria that occurred on day 8 of therapy in one horse; this apparently self-limiting reaction did not necessi-tate discontinuation of treatment.
15
Use in Pregnant Animals and Neonates
The safety of omeprazole paste inpregnant or lactating mares has notbeen determined. Twenty stallions were given omeprazole at 12 mg/kg/dayfor 71 days to investigate its ef-fect on male reproductive safety; noadverse effects on semen quality, tes-ticular volume, or reproductive be-havior were documented.
5
Omepra-zole has been shown to be effectiveand safe for foals as young as 4 weeksof age; no information was found re-garding its safety in younger foals.Because a dose-related increase inembryo death, fetal resorption, andpregnancy disruption occurred in rats
Client Counseling Information
I
Omeprazole is being given to your pet for the treatment and/orprevention of stomach ulcers.
I
This drug has very few side effects in animals; however, notify yourveterinarian immediately if you notice any signs of rash, lethargy, orabnormal bleeding.
I
Try not to miss any doses. If you do, give it as soon as you remember,but never double a dose to make up for a missed dose.
I
Do not give this drug to pregnant animals.
Use of the equine paste syringe:
Omeprazole paste is available in an oral syringe containing sufficientomeprazole for a 1250-lb (568-kg) horse at a dose of 1.8 mg/lb (4 mg/kg).The syringe plunger is marked in 250-lb increments for ease of measuring.To administer the prevention dose (2 mg/kg), the plunger should be set tothe weight corresponding with half the horse’s weight in pounds. Themetered ring is unlocked by turning it one-quarter turn to the left; thisallows the plunger to be set. The ring is then slid to the desired notch andturned one-quarter turn to the right to lock into place.To give omeprazole, first ensure that the horse has no feed in its mouth.Then remove the tip of the syringe, and place the syringe in the interdentalspace. Depress the plunger, and administer the medication to the back of the tongue or deep in the cheek pouch. Briefly observe the horse followingadministration to ensure acceptance of the dose. If any paste is lost,readministration is recommended.Recap the syringe following each administration.
7
Any remainingcontents can be reused as part of the next dose.ed for short-term (i.e., 4 to 8 weeks)treatment of duodenal ulcers, activebenign gastric ulcers, and erosiveesophagitis. Additional indicationsinclude treatment of heartburn andother symptoms associated with gas-troesophageal reflux disease, mainte-nance therapy for healing erosiveesophagitis, and long-term treatmentof pathologic hypersecretory condi-tions; the drug is also used as part of the treatment regimen to eradicate
Helicobacter pylori
infections.
3,4
Omeprazole is used to treat andprevent recurrence of gastric ulcers inhorses older than 4 weeks of age.
7
Al-though not approved for use in dogsand cats, the human formulations of omeprazole are often used to treatmany of the same conditions for which the drug is used in humans.
11,12
The drug has also shown limited prom-ise in treating aspirin- or NSAID-in-duced gastritis, severe esophagitis,gastric ulcers, and gastrinoma.
2,13
Small Animal/Exotics
Compendium
August 2000
and rabbits,
3
omeprazole should beavoided in pregnant dogs and horses.The safety and efficacy of omepra-zole in puppies have not been docu-mented.
ACUTE TOXICITY
The reported LD
50
of omeprazoleis 1.5 g/kg in mice and more than 4g/kg in rats following a single oraldose; at these doses, the animals ex-hibited sedation, ptosis, seizures, de-creased body temperature, and de-creased respiratory rate with shallow respirations.
3
At doses of 125 µmol/kg/day (43.2 mg/kg/day), rats andmice experienced decreased erythro-cyte counts and hematocrit and he-moglobin levels; no clinical signs of toxicity have been reported in rats ordogs after repeated administration.
16
Safety studies with omeprazole pasteshowed no treatment-related adverseeffects in horses when doses of 40mg/kg/day were administered for 21days.
5
In the event of an acute overdose,gut-emptying protocols may be use-ful because absorption does not read-ily occur until the drug has movedout of the stomach. Emesis is not anoption in horses; thus gastric lavageis indicated. Dialysis is not effectivebecause of the high protein-bindingeffect of omeprazole (95%).
3
Sup-portive therapy should be institutedfor patients experiencing any of theaforementioned signs. Diazepam andphenytoin should be used cautiously in patients with seizures; omeprazolecan decrease the hepatic clearance of these drugs, possibly resulting in en-hanced effects or toxicity.
17
DRUG INTERACTIONS
Omeprazole is known to inhibitthe P-450 enzyme system.
3,4
In addi-tion to affecting the metabolism of diazepam and phenytoin, omepra-zole negatively reacts with warfarin;monitoring for signs of toxicity andadjusting dosages may be necessary.In human studies, no dose adjust-ments for theophylline or propran-olol were needed when either of theseagents was administered concurrent-ly with omeprazole.
3,17
Such drugs as ketoconazole, ampi-cillin esters, and iron salts require thepresence of gastric acid to be ab-sorbed properly. Omeprazole thera-py increases gastric pH, which makesconcomitant use of these agents aconcern.
3,4,17
Bone marrow suppres-sion is possible because omeprazole isa benzimidazole derivative; coadmin-istration of agents with similar effectsmay result in an additive effect, andthus careful monitoring is indicated.
17
Another possible interaction thatshould be investigated is whether ad-ministering antacids before omepra-zole can increase gastric pH and thusincrease omeprazole’s bioavailability by promoting earlier absorption.Studies are needed to determine whether omeprazole administered inconjunction with H
2
-blockers ismore effective than giving eitheragent alone. Because administeringboth of these agents is considerably more expensive for owners and morestressful for animals, this considera-tion is important. Efficacy studies in-volving omeprazole and sucralfateare also needed; sucralfate requiresan acid environment to bind to ulcercraters, and this process may theoret-ically be diminished with concurrentuse of omeprazole.
DOSAGE AND ADMINISTRATION
Omeprazole does not have FDA approval for use in dogs; based onavailable literature, however, the rec-ommendedcanine dose for the enteric-coatedomeprazole granules intendedfor human use is 0.7 mg/kg/day. Be-cause doses computed at this ratemay not match available strengthsand because of omeprazole’s relativesafety and tolerability, doses can berounded to 20 mg/day for dogs weighing more than 20 kg and 10mg/day for those weighing less than20 kg.
2,8,17
Anecdotal evidence sug-gests that omeprazole (0.7 mg/kg/day) may be useful in cats, but theliterature does not support these ob-servations.
2,12
Caution should be used when dos-ing omeprazole in horses. Clinicaldata show that the enteric-coated hu-man-labeled granules can be given tohorses at a dose of 1 to 1.5 mg/kg/day. However, the FDA-approvedequine product, designed to deliver 4mg/kg of non–enteric-coated omep-razole, should always be used in horses.This increased dosage was determinedin a study comparing the effects ongastric acid after 5 days of omeprazoleadministered as an injection, enteric-coated granules, or oral paste. Theoriginal paste formulations containedeither the enteric-coated granules oran equipotent uncoated omeprazolepowder. The enteric-coated product(1.5 mg/kg) suppressed acid by 65%and the uncoated powder product(1.5 mg/kg) by 56%; by increasingthe dose to 3 mg/kg, the uncoatedpowder in paste suppressed acid by
TABLE I
Side Effects Associated with Omeprazole versusPlacebo in Humans
3
Reported Frequency (%) Side Effect
OmeprazolePlacebo
Headache6.96.3Upper1.91.6respiratory infectionDizziness1.50Rash1.50Constipation1.10Cough1.10Back pain1.10
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Small Animal/Exotics
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| Upload Date: | 12/07/2009 |
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