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Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia-Cipto
Mangunkusumo Hospital. Jl. Diponegoro no. 71, Jakarta 10430, Indonesia. email: arisyam91@yahoo.com.
ABSTRAK
Tujuan: untuk menilai keamanan dan efikasi dari injeksi lansoprazole (Prosogan®) pada pasien dengan
perdarahan gastrointestinal atas (UGIB) akibat ulkus peptikum atau gastritis erosiva. Metode: suatu studi
observasional pasca-pemasaran lansoprazol injeksi. Pasien dengan UGIB akibat ulkus peptikum atau gastritis
erosiva diberi lansoprazol injeksi selama maksimal 7 hari atau sampai perdarahan berhenti dan pasien dapat
minum lansoprazol oral. Outcome primer studi ini adalah berhentinya perdarahan. Beberapa parameter
laboratorium juga diukur. Hasil: sejumlah 204 pasien dapat dinilai keamanannya, dan tidak ada kejadian tidak
diinginkan yang dilaporkan selama studi. Sejumlah 200 pasien dapat dinilai efikasinya, 125 pasien di antaranya
adalah pasien laki-laki. UGIB berhenti pada 20 pasien (10%) pada hari pertama, 71 pasien (35,5%) pada hari
ke-2, 75 pasien (37,5%) pada hari ke-3, 24 pasien (12,0%) pada hari ke-4, dan 7 pasien (3,5%) pada hari ke-5,
total 197 pasien (98,5%) pada hari ke-5. Efek hemostatik ini dinilai “baik sekali” jika perdarahan berhenti dalam
waktu 3 hari dan “baik” jika perdarahan berhenti dalam waktu 5 hari. Dengan demikian hasilnya baik sekali pada
166 pasien (83,0%) dan baik pada 31 pasien (15,5%). Hasil ini tidak berbeda antara laki-laki dan perempuan,
antara umur di bawah 60 tahun dan 60 tahun ke atas, dan antara Hb awal di bawah 10 g/dL dan 10 g/dL ke atas.
Kesimpulan: hasil studi observasional pasca pemasaran pada 200 pasien dengan UGIB akibat ulkus peptikum
atau gastritis erosiva ini menunjukkan bahwa lansoprazol intravena dua kali sehari aman dan sangat efektif.
Kata kunci: survei pasca-pemasaran, lansoprazole, perdarahan saluran cerna bagian atas.
ABSTRACT
Aim: to assess the safety and effectiveness of lansoprazole injection (Prosogan®) in patients with upper
gastrointestinal bleeding due to peptic ulcers or erosive gastritis. Methods: this study was a multicenter observational
postmarketing study of lansoprazole (Prosogan®) injection. Patients with upper gastrointestinal bleeding due
to peptic ulcers or erosive gastritis were given intravenous lansoprazole for a maximum of 7 days or until the
bleeding stopped and the patients were able to take oral doses of lansoprazole. Primary outcome of the study was
cessation of bleeding. Some laboratory parameters were also measured. Results: among a total of 204 patients
evaluable for safety, there was no adverse event reported during the study. A total of 200 patients were eligible
for efficacy evaluation, 125 patients (62.5%) were males. Among these patients, upper GI bleeding stopped in 20
patients (10.0%) on day 1, in 71 patients (35.5%) on day 2, 75 patients (37.5%) on day 3, 24 patients (12.0%)
on day 4, and 7 patients (3.5%) on day 5, making a cumulative of 197 patients (98.5%) on day 5. The hemostatic
effect was rated as “excellent” if the bleeding stopped within 3 days, and “good” if the bleeding stopped within 5
days. Thus, the results were “excellent” in 166 patients (83.0%) and “good” in 31 patients (15.5%). These results
were not different between males and females, between age below 60 years and 60 years and above, and between
baseline Hb below 10 g/dL and 10 g/dL and above. Conclusion: the results of this observational postmarketing
study in 200 patients with upper gastrointestinal bleeding due to peptic ulcers or erosive gastritis demonstrated
that intravenous lansoprazole twice a day was well tolerated and highly effective.
Key words: postmarketing surveillance (PMS), lansoprazole, upper gastrointestinal bleeding (UGIB).
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Vol 45 • Number 2 • April 2013 Safety and efficacy of Lansoprazole injection in upper GI bleeding
If the UGIB was not caused by peptic ulcers or patients evaluable for safety were 204, while
erosive gastritis, these patients were not included total patients evaluable for efficacy were 200
in the efficacy population, but included in the (4 patients did not meet the inclusion criteria:
safety population. The bleeding stopped if there 3 patients aged <18 years, 1 patient was GERD
was no more hematemesis (the nasal tube fluid patient).
was already clear) and/or melena (the stool was Patient demographics and baseline
not black and liquid anymore). Hemoglobin characteristics are shown in Table 1, vital signs
level was monitored daily depending on the in Table 2, medical history in Table 3, and blood
patient condition. Vital signs and blood chemistry chemistry in Table 4.
were measured again on the last day of therapy.
Concomitant medication was recorded, with the
respective indications. Objective and subjective Table 1. Patient demographics and baseline characteristics
signs and symptoms which emerged during (n=200)
intravenous lansoprazole administration were Median
Variables Mean (SD) Missing
recorded. (Range)
Serious adverse events (AE) were noted: Male: n (%) 125 (62.5%)
death, life-threatening, requires/prolongs Age (yrs) 52.1 (13.34) 55.0 (19 – 70) -
hospitalization, results in persistent/significant Weight (kg) 60.8 (10.39) 60.0 (36 – 100) 1
disability/incapacity, a congenital anomaly/ BMI (kg/m2) 23.0 (3.54) 23.0 (14 – 34) 1
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Ari F. Syam Acta Med Indones-Indones J Intern Med
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Vol 45 • Number 2 • April 2013 Safety and efficacy of Lansoprazole injection in upper GI bleeding
Table 5. Hemostatic effects: total and based on gender 50% were caused by peptic ulcer and erosive
Hemostatic Female gastritis.6
N (%) Male (%)
effect (%) The mortality rate associated with UGIB
Excellent (bleeding remained unchanged around 5-10% for the past
stopped within 3 166 (83.0) 105 (84.0) 61 (81.3)
days)
50 years, despite continuing improvement in
Good (bleeding
the diagnostic and therapeutic modalities.1 This
stopped within 5 31 (15.5) 19 (15.0) 12 (16.0) unchanged mortality rate may be accounted by
days) age and prevalence of concurrent illness, both
Fair (bleeding
are important predictors of death, that continue
stopped within 7 2 (1.0) 1 (1.0) 1 (1.3)
days) to rise among patients with UGIB. Patients with
Poor (bleeding bleeding usually die not from exsanguination,
did not stopped 1 (0.5) - 1 (1.3) but from decompensation due to other diseases.2
within 7 days)
Appropriate initial management is one of the
Total 125 (100.0) 75 (100.0)
key success to reduce morbidity and mortality. In
general, causes of gastrointestinal bleeding were
variceal or non-variceal. A systematic review and
This study showed that lansoprazole injection meta-analysis of 21 randomized controlled trials
could stop bleeding in 10% of cases on day 1, comparing 2915 patients (up to February 2003)
and on day 3 the cumulative stopped bleeding showed that proton pump inhibitor treatment
rate was 83%, increasing to 99.5% after 7 days reduced rebleeding (OR=0.46; 95% CI=0.33-
of treatment. 0.64) and the requirement for surgery (OR=0.59;
The hemostatic effects of lansoprazole 95% CI=0.46-0.76) after ulcer bleeding but did not
injection based on gender were not different reduce mortality (OR=1.11; 95% CI=0.79-1.57).7
(Kolmogorov Smirnov test: Z = 0.183, p = 1.0). Whittle et al.8 have shown that, unlike in the
Based on age groups (<60 years and >60 skin or vasculature, platelet aggregation plays a
years) the hemostatic effects of lansoprazole minimal role in the initial hemostatic events in
injection were also not different (Kolmogorov- the gastric mucosa and that the arrest of gastric
Smirnov test: Z=0.594, p=0.87), neither the hemorrhage is brought about largely by processes
hemostatic effects of lansoprazole injection primarily involving the coagulation system.
based on Hb groups at baseline (Kolmogorov- The stronger drugs suppressing
Smirnov test: Z=0.521, p=0.95). acid production, the better in stopping the
gastrointestinal bleeding. Proton pump inhibitors
DISCUSSION raise the pH to about 6.9 The target therapeutic
In the present study, it was found that 104 goal is to achieve an intragastric pH above 6,
cases (52%) of the 200 UGIB cases were due at which the clotting process is optimal and
to peptic ulcer and 96 cases (48%) to erosive any formed clot is stabilized. The success of
gastritis. Many studies have shown that 50% of hemostasis is highly dependent on the intragastric
the UGIB cases were caused by peptic ulcer.2 pH and studies have shown that, when the intra-
Research conducted at Cipto Mangunkusumo gastric pH is low, platelet function is impaired
Hospital that analyzed patients who presented and pepsinogen is activated to pepsin, which
with upper gastrointestinal bleeding, found that disaggregates platelet plugs.10-11
Table 6. Hemostatic effects based on age group and hemoglobin level at baseline
Hemostatic effect <60 yrs (%) >60 yrs (%) Hb <10 (%) Hb >10 (%)
Excellent 36 (80.0) 130 (83.9) 76 (79.2) 90 (86.5)
Good 8 (17.8) 23 (14.8) 19 (19.8) 12 (11.5)
Fair - 2 (1.3) 1 (1.0) 1 (1.0)
Poor 1 (2.0) - - 1 (1.0)
Total 45 (100.0) 155 (100.0) 96 (100.0) 104 (100.0)
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Ari F. Syam Acta Med Indones-Indones J Intern Med
A meta-analysis of 27 randomized trials of and the duration and severity of bleeding (18.0%
H2-receptor antagonists in over 2500 patients vs. 31.4% with moderate or severe bleeding).16
with acute UIGB suggested that the drugs Bolus i.v. (80 mg) followed by infusion (8
reduced the rates of rebleeding, surgery and mg/h) of omeprazole for 3 days in patients
mortality, by about 10, 20, and 30%, respectively, with bleeding peptic ulcers after endoscopic
notably among those with gastric ulcers.12 In a treatment was also studied by Lau et al.17 and
meta-analysis comparing proton pump inhibitors showed that omeprazole reduced the risk of
with H2 antagonists, it was found that persistent recurrent bleeding (6.7% vs. 22.5% within 30
or recurrent bleeding was less frequent with days; HR=3.9).
proton pump inhibitors (6.7) than with H2 A recent prospective study conducted by
antagonists (13.4%) (OR 0.4; 95%CI: 0.27- Liang et al.18 showed that high-dose pantoprazole
0.59). The need for surgery and mortality rates infusion therapy following endoscopic hemostasis
did not reach statistical significance but showed treatment is not superior to low-dose PPI therapy
a favorable trend towards PPIs.5 in terms of reducing rebleeding among low risk
Mucosal fibrinolytic activity is enhanced in patients with a bleeding peptic ulcer (11.1% in
patients with bleeding gastrointestinal ulcers. each group). A review by van Rensburg and
Acid suppressive therapy reduced this increased Cheer concludes that intravenous pantoprazole is
activity and ultimately decreased bleeding in an effective option in the treatment of UGIB, the
peptic ulcers.13 prevention of rebleeding, and for the prophylaxis
This post-marketing survey showed that of acute bleeding stress ulcers.19
lansoprazole injection could stop upper GI A meta-analysis of 24 randomized controlled
bleeding in 10% of cases on day 1, and 83% trials (4373 participants) through November
of the upper GI bleeding stopped on day 3, 2004 on the efficacy of PPIs for peptic ulcer
increasing to 99.7% after 7 days of treatment. bleeding showed that treatment with PPIs did
This indicates that lansoprazole injection works not reduce mortality (OR=1.01) but significantly
quickly to stop bleeding. The hemostatic effect reduced rebleeding (OR=0.49; 95% CI=0.37-
was rated as excellent if the bleeding stopped 0.65) and the need for surgery (OR=0.61;
within 3 days. Accordingly, this drug was 95% CI=0.48-0.78). Treatment with PPIs
excellent for as much as 83%. These findings significantly reduced mortality in Asian trials
suggest that lansoprazole may be useful in (OR=0.35; 95% CI=0.16-0.74) and in patients
situations where rapid acid control is required, with active bleeding or a nonbleeding visible
such as in emergency care situations. vessel (OR=0.53; 95% CI=0.31-0.91).20 This
A preliminary study using intravenous meta-analysis was the extension of the previous
lansoprazole 30 mg bid in patients with UGIB one7, involving 50% more patients, giving the
for 7 days showed that bleeding was arrested in same results.
16 of 18 patients (89%) within 3 days.14 In this survey, hemoglobin was also
A previous study using oral omeprazole 40 evaluated. During treatment with lansoprazole
mg bid vs. placebo in patients with bleeding injection, hemoglobin level increased. At
peptic ulcers for 5 days showed that omeprazole baseline, hemoglobin level was 9.9 g/dL and rose
therapy was associated with significant reductions to 10.9 g/dL after treatment with lansoprazole
in the rates of further bleeding (10.9% vs. 36.4%) injection. These data demonstrated that during
and surgical intervention (7.2% vs. 23.6%), and administration of lansoprazole, gastrointestinal
the need for transfusion (29.1% vs. 70.9%).15 bleeding did not occur, clinically as well as in the
Another study with bolus i.v. (80 mg) followed laboratory. In several studies, low hemoglobin
by infusion (8 mg/h) of omeprazole vs. placebo value is one predictor of rebleeding.21
for 72 hours in severe ulcer hemorrhage after Several laboratory parameters were also
endoscopic therapy showed that omeprazole examined in this study. The use of lansoprazole
reduced the number of operations (5.4% vs. injection for 1 week did not affect liver function.
11.1%), endoscopic treatments (4.6% vs. 11.1%), Kidney function (creatinine and BUN) was
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Vol 45 • Number 2 • April 2013 Safety and efficacy of Lansoprazole injection in upper GI bleeding
improved during treatment with lansoprazole 9. van Rensburg CJ, Hartmann M, Thorpe A, et al.
injection and these conditions were in line with Intragastric pH during continuous infusion with
pantoprazole in patients with bleeding peptic ulcer.
the cessation of gastrointestinal bleeding.
Am J Gastroenterol. 2003;98:2635-41.
10. Green FW Jr, Kaplan MM, Curtis LE, Levine PH.
CONCLUSION Effect of acid and pepsin on blood coagulation
The results of this observational and platelet aggregation: a possible contributor to
prolonged gastroduodenal mucosal hemorrhage.
postmarketing study in 200 patients with
Gastroenterol. 1978;74(1):38-43.
endoscopically confirmed upper gastrointestinal 11. Berstadt A. Does profound acid inhibition improve
bleeding due to peptic ulcers or erosive gastritis hemostasis in peptic ulcer bleeding. Scand J
demonstrated that intravenous lansoprazole twice Gastroenterol. 1997;32(4):396-8.
a day was well tolerated and highly effective. 12. Collins R, Langman M. Treatment with histamine H2
The authors declare that they have no antagonists in acute upper gastrointestinal hemorrhage:
implications of randomized trials. N Engl J Med.
conflicts of interest in relation to this manuscript.
1985;313:660-6.
13. Vreeburg EM, Levi M, Rauws EAJ, et al. Enhanced
ACKNOWLEDGMENTS mucosal fibrinolytic activity in gastroduodenal
We acknowledge PT. Takeda Indonesia for ulcer haemorrhage and the beneficial effect of acid
suppression. Aliment Pharmacol Ther. 2002;16:1137-
funding this study. We also thank all physicians
42.
who participated in this postmarketing study. 14. Aoki T. Intravenous administration of lansoprazole:
a preliminary study of dose ranging and efficacy in
CONFLICT OF INTEREST UGIB. Aliment Pharmacol Ther. 1995;9(Suppl.1):51-7.
15. Khuroo MS, Yattoo GN, Javid G, et al. A comparison
The authors received grant support from
of omeprazole and placebo for bleeding peptic ulcer.
PT. Takeda Indonesia. N Engl J Med. 1997;336:1054-8.
16. de Muchadell DBS, Havelund T, Harling H, et al.
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