Protoivpump inhibitors for gastric acid-related disease - Cleveland ...
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CURRENT DRUG T H E R A P Y DONALD G. VIDT, MD, EDITOR
THOMAS G. F R A N K O , MS J O E L E. R I C H T E R , MD
Quality assurance clinical specialist, Chairman, D e p a r t m e n t of Gastroenterology,
D e p a r t m e n t of Pharmacy, Cleveland Clinic. Cleveland Clinic, and past president,
American College of Gastroenterology.
Protoivpump inhibitors
for gastric acid-related disease
ROTON-PUMP INHIBITORS, the most effec- ABSTRACT
tive drugs introduced to date for suppress-
ing gastric acid production, have improved the Proton-pump inhibitors are the most effective
treatment of acid-related gastrointestinal dis-
ease.1 Compared with histamine type-2 (H2) drugs introduced to date for suppressing gastric
receptor antagonists, they provide superior heal- acid production. Although they are used to treat
ing rates and symptom relief in peptic ulcer dis-
ease,2-9 reflux esophagitis,10"13 and Zollinger- the same conditions as histamine type-2 receptor
Ellison syndrome.14,15 antagonists, they differ from the latter drugs in
Although the two available proton-pump
inhibitors—omeprazole, approved by the US how they inhibit acid production, and in how they
Food and Drug Administration in 1989, and should be given. Initial concerns over potential ill
lansoprazole, approved in 1995—are used to
treat the same conditions as H2 receptor effects of hypergastrinemia due to long-term acid
antagonists, they differ in how they should be suppression with proton-pump inhibitors have
given. There are also a few minor but note-
worthy differences between the two proton- been unfounded.
pump inhibitors. In the following update we
review the characteristics of proton-pump KEY POINTS
inhibitors and look at how omeprazole and
lansoprazole differ from each other. Proton-pump inhibitors provide superior rates of healing
Another proton-pump inhibitor, panto- and symptom relief compared with histamine type-2
prazole, is available in Europe and is in clini- receptor antagonists. The inhibition of gastric acid secretion
cal trials in the United States for gastro-
is dose-dependent and long-lasting.
esophageal reflux disease and ulcer disease. Its
clinical efficacy appears similar to the other
proton-pump inhibitors. Pending US Food
The adverse effect profile of proton-pump inhibitors is
and Drug Administration approval, pantopra- comparable to that of the histamine type-2 receptor
zole should be available in the next 2 years. antagonists.
Perprazole, an optical isomer of omepra-
zole, is also under investigation. It is purport- Proton-pump inhibitors are given once daily. Taking liquid
ed to have unique pharmacokinetic properties antacids concomitantly does not affect omeprazole
that may lead to rapid resolution of symptoms absorption.
and high, predictable healing rates. A new
drug application is expected to be filed within
the next 2 years. Perprazole will be available
in a new oral dosage form called the "multi-
unit pellet system." This is a tablet that is eas-
ier to swallow because it can be halved or dis-
solved in water for liquid dosing.
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PROTON-PUMP INHIBITORS FRANKO AND RICHTER
• HOW DO PROTON-PUMP INHIBITORS WORK? H o w p r o t o n - p u m p inhibitors c o m p a r e
w i t h h i s t a m i n e - 2 receptor antagonists
Instead of blocking the primary stimuli of Proton-pump inhibitors provide superior heal-
gastric acid secretion (ie, food, gastrin, hista- ing rates and symptom relief compared with
mine), the proton-pump inhibitors directly H 2 receptor antagonists.
block the final step of gastric acid produc- • In patients with duodenal and gastric
tion, ie, the hydrogen-potassium ATPase16 ulcer, 4-week healing rates were 69% to 100%
enzyme system on the secretory surface of in clinical trials, compared with 58% to 89%
gastric parietal cells—the "acid (proton) for H 2 receptor antagonists.2-9
pump" ( F I G U R E 1 ) . • In reflux esophagitis, 8-week healing
The inhibition of gastric acid secretion rates were 70% to 92%, compared with 29%
caused by proton-pump inhibitors is dose- to 70% for H 2 receptor antagonists.10-13
dependent and long-lasting, because these • In Zollinger-Ellison syndrome,15-16 a
drugs bind permanently to hydrogen-potassium gastric acid output of less than 10 mmol/hour
ATPase molecules. Because secretion of acid before the next dose is given is universally
can resume only after new molecules of hydro- accepted as the guide to effectiveness of thera-
gen-potassium ATPase are generated, the inhi- py. Relief of symptoms is an unreliable guide.
bition persists long after the drug is cleared Gastric acid secretion can be controlled (
M Acid production and inhibition
in the gastric parietal cell
MuscarinicNJp
receptor M g .
Proton-
astrin
?ceptc ( H+, K+ \
ATPase
(proton pump);
Histamine
type-2
receptor
ine type-2 \
Dr a n t a g o n i s t s
FIGURE 1. Rather than block one or another of the primary stimuli of gastric
acid production (eg, histamine, gastrin, muscarinic receptors), proton-pump
inhibitors stop acid secretion by inhibiting the final common pathway of
acid production: the acid proton pump, hydrogen-potassium ATPase, on the
surface of the gastric parietal cell. In contrast, anticholinergic drugs block
muscarinic receptors, which normally activate the proton pump via the
calcium-dependent pathway. Histamine type-2 receptor antagonists block
histamine receptors, which normally activate the proton pump via the cyclic
adenosine monophosphate (cAMP) pathway. Antacids interact with
hydrochloric acid to increase the gastric pH; gastric acid activity decreases as
the pH rises.
C L E V E L A N D C L I N I C J O U R N A L OF M E D I C I N E V O L U M E 65 • N UMBER 1 JANUARY 1998 2 9
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PROTON-PUMP INHIBITORS FRANKO AND RICHTER
In addition to these, a few cases of skin 8 DRUG INTERACTIONS
rash have been reported (0.5% to 1%).32'33
Idiosyncratic adverse effects were also report- O m e p r a z o l e drug interactions
ed: gynecomastia, 3 cases; lichen planus, 1 Omeprazole can bind to hepatic
case; subacute myopathy, 1 case; sexual distur- cytochrome P450 I I C and inhibit the
bances, 2 cases; renal failure, 1 case; acute oxidative metabolism of diazepam and
interstitial nephritis, 1 case; and fulminant phenytoin, leading to increased plasma lev-
hepatic failure, 1 case.34 Fewer than 2% of els of these drugs. However, the omepra-
patients treated with omeprazole have with- zole-diazepam and omeprazole-phenytoin
drawn from clinical trials because of adverse interactions are of limited clinical signifi-
events. The adverse event profile of long-term cance. Furthermore, since few drugs are
omeprazole use (up to 6 years) was reported to metabolized mainly by cytochrome P450
be similar to that of short-term omeprazole IIC, the potential for omeprazole to inter-
therapy.31 fere with the metabolism of other drugs
appears to be limited.to
Lansoprazole side effects Omeprazole also appears to inhibit the
Patients have received lansoprazole for up to 4 hepatic metabolism of the R-isomer of war-
years in clinical trials without experiencing farin (which is pharmacologically less active
significant adverse effects. Lansoprazole is than the S-isomer), resulting in a slight
clinically well tolerated. The most common increase in anticoagulation activity. As with
reported adverse reactions35 are gastrointesti- the interactions cited above, studies show that
nal: diarrhea 3.2%, abdominal pain 2.2%, this is not likely to be of clinical signifi-
nausea 1.4%, and constipation 1.1%. Central c a n c e , 4 1 . 4 2 but a single case report indicates
nervous system reactions are the next most that certain individuals may exhibit clinically
frequently reported, with headache 4.7% and important increases.43
dizziness 1%. As with omeprazole, skin disor- Proton-pump inhibitors can inhibit the
ders such as rash and pruritus have also been absorption of drugs such as griseofulvin, keto-
reported in 1.7% of patients. conazole, itraconazole, iron salts, and
Omeprazole and Increases in liver enzymes, hemoglobin, cyanocobalamin, which require acid for
hematocrit, urinary protein excretion, and absorption. Conversely, drugs normally
lansoprazole are uric acid levels have been reported. Fewer destroyed by gastric acid (penicillin, didano-
well tolerated, than 1.2% of patients treated with lansopra- sine) may show increased absorption.
zole withdrew because of adverse events.35 Interaction with clarithromycin. Con-
with an comitant administration of omeprazole and
incidence of Concerns over l o n g - t e r m t r e a t m e n t clarithromycin may result in increased serum
A consequence of the rigorous inhibition of concentrations of both drugs. Also, the gastric
adverse effects gastric acid secretion produced by proton- mucous concentration of clarithromycin may
similar to those pump inhibitors is achlorhydria, the absence be increased. Clarithromycin may inhibit the
of free hydrochloric acid. There was concern metabolism (via cytochrome P450 IIIA4) of
of H 2 receptor early on that sustained achlorhydria induced omeprazole, while omeprazole may increase
antagonists by proton-pump inhibitors could result in ele- the absorption of clarithromycin. The con-
vated serum gastrin concentrations, which in comitant administration of these agents may
turn could produce carcinoid tumors; howev- be beneficial in the treatment of H pylori
er, this has not been shown to be a problem, infections. No adjustment in dosage is neces-
either with long-term omeprazole use in the sary for either agent.tt
United States or with long-term lansoprazole
use in Europe.36 Achlorhydria produced by Lansoprazole drug interactions
proton-pump inhibitors has led to hypergas- The metabolism of lansoprazole also involves
trinemia and carcinoid tumors only in rats; the hepatic cytochrome P450 enzyme system,
these findings have not been shown to occur but lansoprazole does not appear to signifi-
in other animal species (humans, dogs, guinea cantly interact with other drugs metabolized
pigs, hamsters, mice).37"39 by this system.45
30 C L E V E L A N D C L I N I C J O U R N A L OF M E D I C I N E V0 L U M E 6 5 • N U M B ER 1 JANUARY 1998
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TABLE 1
Dosage recommendations for proton-pump inhibitors
INDICATION OMEPRAZOLE LANSOPRAZOLE
Duodenal ulcer 20 mg/day up to 4 weeks 15 mg/day up to 4 weeks
Gastric ulcer 20 mg/day up to 8 weeks 30 mg/day up to 8 weeks
Reflux esophagitis
Short-term therapy 20 mg/day up to 8 weeks 30 mg/day up to 8 weeks
Maintenance therapy 20 mg/day 15 mg/day
Resistant ulcer 40 mg/day up to 8 weeks* 30 mg/day up to 8 weeks
Zollinger-Ellison s y n d r o m e t 60 mg/day§ 60 mg/day*
"Twice-daily dosing (doses > 40 mg/day) provides better gastric acid suppression compared with once-daily
dosing 5 0
f Titrate for a basal acid output < 10 mmol/h prior to next dose
•May be increased up to 90 mg twice daily if necessary
§May be increased up to 180 mg twice daily if necessary
mmm
No clinically significant interactions have • DOSAGE A N D A D M I N I S T R A T I O N
been reported to date in the 2 years since lan-
soprazole has been available in the United Proton-pump inhibitors are long-acting, per-
States. As described above with omeprazole, mitting once-daily dosing. Both omeprazole
lansoprazole may adversely affect medications and lansoprazole are available as delayed-
requiring acid for absorption, while increasing release capsules.
absorption of medications normally destroyed Omeprazole is available as 10- and 20-mg
by gastric acid. capsules. It is Lisually given in the morning
before breakfast. The recommended dosages
• BIOAVAILABILITY are 20 mg daily for 2 to 8 weeks for reflux
esophagitis or duodenal or gastric ulcers. A
Omeprazole bioavailability46 increases with dosage of 40 mg daily may be required in
repeated administration, suggesting that patients with conditions poorly responsive to
either absorption increases or first-pass hepat- H 2 receptor antagonists or in patients in whom
ic metabolism becomes saturated, or both. ulcers have not healed with omeprazole 20 mg
Food delays the rate, but not the extent, of daily (TABLE 1 ) . With higher doses (40 mg per
omeprazole absorption. Concomitant admin- day or more), a twice-daily dosing regimen
istration with liquid antacids has no effect on (before breakfast and dinner) may provide bet-
omeprazole absorption. ter acid control than once-daily dosing.4?
Lansoprazole bioavailability decreases For patients with Zollinger-Ellison syn-
27% when given with a meal,45 but gastric drome, omeprazole 60 mg given daily and
acidity reduction was found to be similar titrated to patient response is recommended,
whether lansoprazole was given 30 minutes although lower doses (10 to 40 mg per day)
before or 30 minutes after a meal for 7 days. are effective. For complicated reflux esophagi-
Concomitant administration of antacids tis, omeprazole 20 mg daily is approved for
resulted in a small decrease in lansoprazole long-term maintenance therapy. Dosage
absorption. Concurrent administration of lan- reductions have not been reported necessary
soprazole and sucralfate reduced lansoprazole's in patients with hepatic or renal impairment,
bioavailability by 30%. or in the elderly.
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PROTON-PUMP INHIBITORS FRANKO AND RICHTER
Lansoprazole is available as 15-mg and idazole or amoxicillin.
30-mg capsules. Like omeprazole, it is general- After the ulcer has healed, confirming H
ly given in the morning before breakfast. The pylori infection is optional in patients with
recommended dosage is 15 or 30 mg daily for no complications. Patients with bleeding
2 to 8 weeks for reflux esophagitis or duodenal and postoperative patients should be retest-
or gastric ulcer ( T A B L E 1 ) . In lesions refractory to ed. H pylori infection is best confirmed by
H2 receptor antagonist therapy, lansoprazole the newly available urea breath test
30 to 60 mg per day for 8 to 12 weeks may be (Meretek Diagnostics, Nashville, TN; Tri-
required. Lansoprazole 60 tng daily titrated to Med Specialties, Charlottesville, VA). After
patient response (15 to 180 mg per day) is ulcer healing and H pylori eradication, the
effective in Zollinger-Ellison syndrome. For proton-pump inhibitor can be stopped.
complicated reflux esophagitis, lansoprazole Lansoprazole has been reported to signifi-
15 mg daily is approved for long-term mainte- cantly affect the accuracy of the MC-urea
nance therapy. Lansoprazole 30 mg daily was breath test (Tri-Med Specialties) by a pH-
reported not to be more effective than 15 mg dependent mechanism causing equivocal or
daily for maintenance t h e r a p y . 4 8 No dosage false-negative results in 61% of patients.50
adjustment has been reported to be necessary Proton-pump inhibitors should be stopped at
in patients with hepatic or renal impairment, least 5 days before testing, or as recommended
or in the elderly. by the test manufacturer.
Fewer than 8% of H pylori'negative
Advising patients patients experience ulcer recurrence within 1
on h o w to t a k e the capsules year after all acid-suppressive therapy has been
Omeprazole and lansoprazole are stable at neu- discontinued.51
tral pH, but are destroyed by gastric acid.
Therefore, patients not able to swallow cap- Reducing t h e risk of gastric a t r o p h y
sules may be instructed to break open the In patients with gastroesophageal reflux dis-
gelatin-coated capsule and mix the contents ease and H pylori infection, long-term therapy
with a small amount of fruit juice or applesauce with a proton-pump inhibitor can result in
Proton-pump immediately before oral administration. more severe gastritis and, after 5 years of treat-
Patients should be advised not to crush the ment, can lead to gastric atrophy in 31% of
inhibitors
enteric-coated grains by stirring or chewing, as patients. Gastric atrophy is thought to be an
directly block this exposes the drug to premature breakdown essential step in the cascade of events leading
by gastric acid in the stomach.49 to gastric cancer. H pylori detection and eradi-
the final step
cation are therefore indicated in patients with
of gastric acid • THE ROLE OF PROTON-PUMP INHIBITORS gastrointestinal esophageal reflux disease who
IN H PYLORI ERADICATION will be undergoing long-term treatment with a
production
proton-pump inhibitor.52
Duodenal or gastric ulcers unrelated to the
use of nonsteroidal anti-inflammatory drugs • THE AUTHORS' PERSPECTIVE
are most often related to H pylori infection.
All patients with active ulcer disease should Proton-pump inhibitors are a major advance
be tested for H pylori infection, by blood in the treatment and management of acid-
serology or by tissue sampling at the time of related disease. Superior healing and symptom
endoscopy for histologic c x a L n i n a t i o n or relief, including relief in those conditions
urease test for H pylori. If infection is found, poorly responsive to H2 receptor antagonist
treatment should be started with: therapy, make them agents of choice. Proton-
• A n acid-suppressing drug, to allow the pump inhibitors have demonstrated a short-
ulcer to heal. and long-term safety profile similar to that of
• A double-drug or triple-drug antibiotic H2 receptor antagonists.
regimen to eradicate H pylori. Examples are Proton-pump inhibitors cost more than
tetracycline plus metronidazole and bismuth H 2 receptor antagonists ( T A B L E 2 ) , but they
subsalicylate, or clarithromycin plus metron- appear to be more cost-effective due to their
32 C L E V E L A N D C L I N I C J O U R N A L OF M E D I C I N E V 0 L U M E 6 5 • N U M B ER 1 JANUARY 1998
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superior efficacy in short-term treatment of TABLE 2
duodenal and gastric ulcer, as well as short-
and long-term treatment of complicated Cost of p r o t o n - p u m p inhibitors
reflux esophagitis.53-55 The improved cost- compared with histamine type-2
effectiveness is due to shorter treatment peri- receptor antagonists
ods and lower follow-up costs associated with
MEDICATION DOSAGE COST*
treatment failures. Compared with each 4 WEEKS 8 WEEKS
other, lansoprazole and omeprazole appear to
be equally safe and effective. Lansoprazole Histamine type-2 receptor antagonists
may be somewhat less expensive than
Cimetidine^ 800 mg/day $83.65 $167.30
omeprazole (TABLE 2 ) .
Proton-pump inhibitors are gradually Famotidine 40 mg/day $95.86 $191.72
replacing H2 receptor antagonists in the Nizatidine 300 mg/day $96.00 $192.00
physician's armamentarium for the treatment
of acid-related diseases. This evolution has Ranitidine^ 300 mg/day $88.80 $177.60
been hastened by the ready availability of Proton-pump inhibitors
over-the-counter H 2 receptor antagonists. H 2
Lansoprazole 30 mg/day $102.68 $205.36
receptor antagonists may still be a reasonable
alternative in patients with gastroesophageal 15 mg/day $100.75 $201.50
reflux disease characterized by mild symptoms
Omeprazole 20 mg/day $108.90 $217.80
and minimal to no esophagitis or mild,
uncomplicated peptic ulcer disease. Ü 10 mg/day $97.56 $195.12
• REFERENCES 'Average wholesale price, Red Book, 1996
'Generic product
1. Hetzel DJ, Shearman DJC. O m e p r a z o l e inhibition of noc-
t u r n a l gastric secretion In patients w i t h d u o d e n a l ulcer.
Br J Clin Pharm 1984; 18:587-590.
2. Bardhan KD, Bianchi Porro G, Bose K, et al. Comparison
of t w o different doses of o m e p r a z o l e versus ranitidine In of elderly and young patients w i t h reflux esophagitis.
d u o d e n a l ulcer healing. Gut 1985; 2 6 : A 5 5 7 - A 5 5 8 . A g e Aging 1994; 23:121-126.
3. Lauritsen K, Rune SJ, Bytzer P, et al. Effect of o m e p r a z o l e 12. Hazenburg BP, Geraedts A A M , de Groot GH. O m e p r a z o l e
a n d Cimetidine on duodenal ulcer. N Engl J M e d 1985; versus ranitidine in t h e t r e a t m e n t of symptomatic mild
312:958-961 reflux esophagitis: A Dutch multi-center trial [abstract].
4. Hotz J, Kleiner R, G r y m b o w s k i T, e t al. Lansoprazole ver- Gut 1994; 35 Suppl 2:W26.
sus famotidine: efficacy and tolerance In t h e acute m a n - 13. Robinson M , Sahba B, Avner D, et al. A comparison of
a g e m e n t of duodenal ulceration. A l i m e n t Pharmacol lansoprazole and ranitidine In t h e t r e a t m e n t of erosive
Ther 1992; 6:87-95. esophagitis. A l i m e n t Pharmacol Ther 1995; 9:25-31.
5. Londong W, Barth H, D a m m a n n HG, et al. Dose related 14. Jensen RT, Fraker DL. Zollinger-Ellison syndrome.
healing of duodenal ulcer w i t h t h e proton p u m p inhibitor Advances in t r e a t m e n t of gastric hypersecretion and t h e
lansoprazole Aliment Pharmacol Ther 1991; 5:245-254. gastrinoma. J A M A 1994; 271:1429-1435.
6. Bate C M , Wilkinson SP, Bradley GVH, e t al. Randomized, 15. Jensen RT, M e t z PD, Feigenbaum K M . A prospective
d o u b l e blind comparison of omeprazole and Cimetidine study of t h e long-term efficacy and safety of lansopra-
In t h e treatment of symptomatic gastric ulcer. Gut 1989; zole In patients w i t h t h e Zollinger-Ellison syndrome.
30:1323-1328. Aliment Pharmacol Ther 1993; 7:41-50.
7. Lauritsen K, Rune SJ, W u l f f HR, et al. Effect of omepra- 16. Elander B, Fellenius E, Leth R, et al. Inhibitory action of
zole a n d Cimetidine on prepyloric gastric ulcer: double- omeprazole on acid f o r m a t i o n in gastric glands and on
blind comparative trial. Gut 1988; 29:249-253. HIP|u!), KIpM-ATPase Isolated f r o m h u m a n gastric mucosa.
8. W a l a n A, Bader J-P, Classen M , et al. Effect of o m e p r a - Scand J Gastroenterol 1986; 21:268-272.
zole a n d ranitidine on ulcer healing and relapse rates in 17. Bardhan KD, Naesdal J, Bianchi Porro G, et al. Treatment
patients with benign gastric ulcer. N Engl J M e d 1989; of refractory peptic ulcer disease w i t h omeprazole or
320:69-75. continued H 2 receptor antagonists: a controlled clinical
9. Michel P, Lemaire M , Colin R, et al. Treatment of gastric trial. Gut 1991; 32:435-438.
ulcer w i t h lansoprazole or ranitidine: a multicenter clini- 18. Delle Fave G, Annlbale B, Helander H, et al. O m e p r a z o l e
cal trial. Aliment Pharmacol Ther 1994; 8:119-122. versus high-dose ranitidine in H 2 -blocker resistant duode-
10. Bianchi Porro G, Pace F, Peracchia A, et al. Short t e r m nal ulcer patients. Eur J of Gastroenterol Hepatol 1991;
t r e a t m e n t of refractory reflux esophagitis w i t h d i f f e r e n t 3:337-342.
doses of omeprazole or ranitidine. J Clin Gastroenterol 19. Delchier J-C, Isal J-P, Eriksson S, e t al. Double blind multi-
1992; 15:192-198. centre comparison of omeprazole 20 m g once daily ver-
11. James OFW, Parry-Billings KS. Comparison of o m e p r a z o l e sus ranitidine twice dally In t h e t r e a t m e n t of cimetidine
a n d histamine H 2 -receptor antagonists In t h e t r e a t m e n t or ranitidine resistant duodenal ulcers. Gut 1989;
C L E V E L A N D C L I N I C J O U R N A L OF M E D I C I N E V O L U M E 65 • N UMBER 1 JANUARY 1998 3 3
Downloaded from www.ccjm.org on November 28, 2021. For personal use only. All other uses require permission.
PROTON-PUMP INHIBITORS FRANKO AND RICHTER
30:1173-1178. of antiulcer drugs. Drug Safety 1995; 12:120-138.
20. Brunner G, Arnold R, Hennig U, et al. A n open trial of 35. Colin-Jones DG. Safety of lansoprazole. A l i m e n t
long-term therapy w i t h lansoprazole in patients with pep- Pharmacol Ther 1993; 7 Suppl 1:41-50.
tic ulceration resistant t o extended high dose ranitidine 36. Freston JW. Long-term acid control and p r o t o n p u m p
treatment. Aliment Pharmacol Ther 1993; 7 Suppl 1:51-55. inhibitors: Interactions and safety issues in perspective.
21. Feldman M , Harford WV, Fisher RS, et al. Treatment of A m J Gastroenterol 1997; 92(4):51S-55S.
reflux esophagitis resistant t o H 2 -receptor antagonists 37. Pension J, Wormsley KG. Achlorhydria; hypergastrinemia;
w i t h lansoprazole, a n e w H l p M / K l p M - a t p a s e inhibitor: a carcinoids—a f l a w e d hypothesis. G u t 1987; 28:488-505.
controlled, double blind study. A m J Gastroenterol 1993; 38. Freston JW. Clinical significance of hypergastrinemia:
88:1212-1217. Relevance t o gastrin monitoring during o m e p r a z o l e ther-
22. Robinson M , Campbell DR, Sontag S, et al. Treatment of apy. Digestion 1992; 51(1 ):102-114.
erosive reflux esophagitis resistant t o H 2 -receptor antago- 39. Karnes WE, Walsh JH. The gastrin hypothesis: Implications
nist therapy—lansoprazole, a n e w proton p u m p inhibitor. for antisecretory drug selection. J Clin Gastroenterol
Digest Dis Sciences 1995; 4 0 : 1 - 8 . 1990; 12(2):S7-12.
23. Bardhan KD, Morris P, T h o m p s o n M, et al. Omeprazole in 40. Andersson T. Omeprazole d r u g interaction studies. Clin
t h e t r e a t m e n t of erosive esophagitis refractory t o high Pharmacokinet 1991; 21:195-212.
dose cimetidine and ranitidine. Gut 1990; 31:745-749. 41. Sutfin T, Balmer K, Bostrom H, Eriksson S, Hoglund P,
24. Dent J, Klinkenberg-Knol EC, Elin G, et al. O m e p r a z o l e in Paulsen O. Stereoselective interaction of omeprazole w i t h
t h e long-term m a n a g e m e n t of patients w i t h reflux warfarin in healthy men. Therapeutic D r u g M o n i t o r i n g
esophagitis refractory t o histamine H 2 -receptor a n t a g o - 1989; 11:176-184.
nists (abstract). Scand J Gastroenterol 1989; 24(Suppl 42. U n g e P, Svedberg LE, Nordgren A, et al. A study of t h e
166):176. interaciton of omeprazole a n d w a r f a r i n in anticoagulated
25. Koop H, Hotz J, Pommer G, et al. Prospective evaluation patients. Br J Clin Pharmacol 1992; 34:509-512.
of omeprazole t r e a t m e n t in reflux esophagitis refractory 43. A h m a d S. Omeprazole-warfarin interaciton [letter], S
to H 2 -receptor antagonists. Aliment Pharmacol Ther 1990; M e d J 1991; 84:674-675.
4:593-599. 44. Gustavson LE, Kaiser JF, Edmonds AL, Locke CS,
26. Lundell L, Backman L, Ekstrom P, et al. Prevention of DeBartolo ML, Schneck DW. Effect of o m e p r a z o l e on con-
relapse of reflux esophagitis after endoscopic healing: t h e centrations of clarithromycin in plasma a n d gastric tissue
efficacy and safety of omeprazole compared w i t h raniti- at steady state. Antimi:rob Agents C h e m o t h e r 1995;
dine. Scand J Gastroenterol 1991; 248-256. 39:2078-2083.
27. Marciano-D'Amore DA, Paterson W G , Da Costa LR, et al. 45. Delhotal Landes B, Petite JP, Flouvat B. Clinical pharmaco-
Omeprazole in H 2 -receptor antagonist-resistant reflux kinetics of lansoprazole. Clin Pharmacokinet 1995;
esophagitis. J Clin Gastroenterol 1990; 12:616-620. 28:458-470.
28. Vigneric S, Termini R, Leandro G, et al. A comparison of 46. H o w d e n CW. Clinical pharmacology of omeprazole. Clin
five maintenance therapies for reflux esophagitis. N Engl Pharmacokinet 1991; 20:38-49.
J M e d 1995; 333:1106-1110. 47. Kuo B, Castell DO. Optimal dosing of o m e p r a z o l e 40 mg:
29. Klinkenberg-Knol EC, Festen HPM, Jansen JBMJ, et al. The effects on gastric and esophageal pH a n d serum gastrin
efficacy and safety of long-term t r e a t m e n t w i t h omepra- in healthy controls. Am J Gastroenterol 1996;
zole of patients w i t h refractory reflux esophagitis. A n n 91:1532-1538.
Intern M e d 1994; 121:161-167. 48. Robinson M , Lanza F, Avner D, et al. Effective mainte-
30. Solwell L. The clinical safety of omeprazole. Digestion nance t r e a t m e n t of reflux esophagitis w i t h low dose lan-
1990; 47 Suppl 1:59-63. soprazole. A randomized, double-blind, placebo con-
31. Joelson S, Joelson B, Lindberg P, et al. Safety experience trolled trial. A n n Intern M e d 1996; 124:859-867.
f r o m long-term t r e a t m e n t w i t h omeprazole. Digestion 49. Chun AH, Eason CJ, Shi HH, C a v a n a u g h JH. Lansoprazole:
1992; 51 Suppl 1:93-101. a n alternative m e t h o d of administration of a capsule
32. Simon TJ, Bradstreet DC. Comparative tolerability profile dosage formulation. Cin Ther 1995; 17:441-447.
of omeprazole in clinical trials. Dig Dis Sci 1991; 50. Chey W D , Woods M, Scheiman JM, Nostrant TT, DelValle
36:1384-1389. J. Lansoprazole and ranitidine affect t h e accuracy of t h e
33. Bamberg P, Caswell CM, Frame M H , et al. Alimentary 14C-urea breath test by a p H - d e p e n d e n t mechanism. A m
tract and pancreas. A meta analysis comparing t h e effica- J Gastroenterol 1997; 92:446-450.
cy of omeprazole w i t h H 2 -receptor antagonists for acute 51. Seppala K, Pikkarainen P, Sipponen P, et al. Cure of peptic
t r e a t m e n t of duodenal ulcer in Asian patients. J ulcer associated w i t h eradication o f Helicobacter pylori.
Gastroenterol Hepatol 1992; 7:577-585. Finnish Gastric Ulcer Study Group. Gut 1995; 8 3 4 - 8 3 7 .
34. Piper DW. A comparative overview of t h e adverse effects 52. Kuipers EJ, Lundell L, Klinkenberg-Knol EC, e t al. Atrophic
gastritis and Helicobacter pylori infection in patients w i t h
reflux esophagitis treated w i t h o m e p r a z o l e or fundopli-
cation. N Engl J M e d 1996; 3 3 4 : 1 0 1 8 - 1 0 2 2 .
53. Lindberg G. Omeprazole vs ranitidine in reflux esophagi-
tis in Sweden. Pharmacoeconomics 1994; 5 Suppl 3:27-34.
I B One Hour Category I CME Credit 54. Bate CM. Omeprazolevs ranitidine and cimetidine in
reflux esophagitis—the British perspective.
is now available ONUNEjat the Pharmacoeconomics 1994; 5 Suppl 3:34-43.
55. Jonsson B, D r u m m o n d MF, S t a l h a m m a r N. Cost-effective-
Cleveland Clinic Journal of Medicine ness of omeprazole and ranitidine in t h e t r e a t m e n t of
duodenal ulcer. Pharmacoeconomics 1994; 5 Suppl
Web site: www.ccf.org/pc/gim/cme/opencme.htm 3:44-55.
ADDRESS: Thomas G. Franko, MSC, S107, The Cleveland Clinic
Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, e-mail
frankot@cesmpt.ccf.org.
34 C L E V E L A N D C L I N I C J O U R N A L OF M E D I C I N E V0 L U M E 6 5 • N U M B ER 1 JANUARY 1998
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