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SafetyandEfficacyofLansoprazoleInjectioninUpperGastrointestinal
Bleeding:apostmarketingsurveillanceconductedinIndonesia.

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 ORIGINALARTICLE

Safety and Efficacy of Lansoprazole Injection

in Upper Gastrointestinal Bleeding:
a Postmarketing Surveillance Conducted in Indonesia

Ari F. Syam1, Arini Setiawati2,3

1
DepartmentofInternalMedicine,FacultyofMedicine,UniversityofIndonesia-CiptoMangunkusumoHospital,
Jakarta, Indonesia. 2 Clinical Study Unit, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
3
DepartmentofPharmacologyandTherapeutics,FacultyofMedicine,UniversityofIndonesia,Jakarta,Indonesia.

Correspondence mail:
DivisionofGastroenterology,DepartmentofInternalMedicine,FacultyofMedicine,UniversityofIndonesia-Cipto
MangunkusumoHospital.Jl.Diponegorono.71,Jakarta10430,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
observasionalpasca-pemasaranlansoprazolinjeksi.PasiendenganUGIBakibatulkuspeptikumataugastritis
erosivadiberilansoprazolinjeksiselamamaksimal7hariatausampaiperdarahanberhentidanpasiendapat minum
lansoprazol oral. Outcome primer studi ini adalah berhentinya perdarahan. Beberapa parameter
laboratoriumjugadiukur.Hasil:sejumlah204pasiendapatdinilaikeamanannya,dantidakadakejadiantidak
diinginkanyangdilaporkanselamastudi.Sejumlah200pasiendapatdinilaiefikasinya,125pasiendiantaranya
adalahpasienlaki-laki.UGIBberhentipada20pasien(10%)padaharipertama,71pasien(35,5%)padahari ke-
2,75pasien(37,5%)padaharike-3,24pasien(12,0%)padaharike-4,dan7pasien(3,5%)padaharike-5,
total197pasien(98,5%)padaharike-5.Efekhemostatikinidinilai“baiksekali”jikaperdarahanberhentidalam
waktu3haridan“baik”jikaperdarahanberhentidalamwaktu5hari.Dengandemikianhasilnyabaiksekalipada
166pasien(83,0%)danbaikpada31pasien(15,5%).Hasilinitidakberbedaantaralaki-lakidanperempuan,
antaraumurdibawah60tahundan60tahunkeatas,danantaraHbawaldibawah10g/dLdan10g/dLkeatas.
Kesimpulan:hasilstudiobservasionalpascapemasaranpada200pasiendenganUGIBakibatulkuspeptikum atau
gastritis erosiva ini menunjukkan bahwa lansoprazol intravena dua kali sehari aman dan sangatefektif.

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
gastrointestinalbleedingduetopepticulcersorerosivegastritis.Methods:thisstudywasamulticenterobservational
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
bleedingstoppedandthepatientswereabletotakeoraldosesoflansoprazole.Primaryoutcomeofthestudywas
cessationofbleeding.Somelaboratoryparameterswerealsomeasured.Results:amongatotalof204patients
evaluable for safety, there was no adverse event reported during the study. A total of 200 patients were eligible
forefficacyevaluation,125patients(62.5%)weremales.Amongthesepatients,upperGIbleedingstoppedin20
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%)
onday4,and7patients(3.5%)onday5,makingacumulativeof197patients(98.5%)onday5.Thehemostatic

ActaMedicaIndonesiana-TheIndonesianJournalofInternalMedicine
123
 AriF. ActaMedIndones-
PENGANTAR
Pendarahan saluran cerna bagian atas (UGIB) adalah penyakit berat yang mengancam jiwa dengan tingkat kematian yang tetap konstan pada 5 hingga
10%, selama 50 tahun terakhir. Ulkus peptikum adalah penyebab paling umum dari UGIB, terhitung sekitar 50% dari kasus. 2
Perawatan medis perdarahan ulkus diarahkan untuk menjaga pH lambung di atas kisaran proteolitik untuk pepsin. 3 Peningkatan pH toksikjuik untuk
meningkatkan metabolisme aktivitas fibrinolitik dalam jus lambung.4. Menjaga pH lambung di atas rentang proteolitik untuk pepsin dalam perdarahan,
proton parenteral inhibitor pompa terbukti lebih efektif daripada antagonis histamin H2 parenteral. 3,5 Lansoprazoleinjeksi merupakan PPI intravena
terbaru yang tersedia di Indonesia. Oleh karena itu, diperlukan studi pasca pemasaran untuk memantau keamanan dan efektivitasnya dalam praktik
klinis.
Subjek umum tidak memiliki tingkat keamanan dan keefektifan injeksi lansoprazole pada pasien yang mengalami perusakan usus, karena
topepticulcoreratorpenyakit ginjal. Sasaran spesifik adalah untuk menilai keamanan berdasarkan pada tanda dan gejala objektif dan subyektif, dan
kelainan tes fungsi hati dan untuk menilai keefektifan uji fungsi hati.

METODE
Desain dan Pasien
Ini adalah penelitian observasional, multisenter, postmarketing pada pasien dengan perdarahan gastrointestinal bagian atas karena tukak lambung atau
gastritis erosif yang menerima lansoprazole intravena selama maksimal 7 hari atau sampai perdarahan berhenti dan pasien dapat mengambil
lansoprazole oral.

Pasien yang direkrut adalah mereka yang datang ke ruang gawat darurat (UGD) sebuah rumah sakit dengan hematemesis dan / atau melena, dan
memenuhi kriteria inklusi termasuk dalam kriteria inklusi. Total 200 pasien yang direncanakan untuk dikendalikan dari 100 dokter spesialis penyakit
dalam di Indonesia. Pasien dengan perdarahan gastrointestinal bagian atas dianggap memenuhi syarat jika mereka memenuhi kriteria inklusi berikut: (i)
Pria atau wanita dengan gastrointestinalbleeding (UGIB) karena ulkus peptikum atau gastritis erosif, (ii) berusia 18 tahun hingga 70 tahun, tidak
termasuk dalam penelitian. Pasien tidak termasuk dalam studi jika mereka secara hemodinamik tidak stabil. (hipotensi, takikardi, atau perubahan postur
jantung atau tekanan darah), hipersensitif terhadap lansoprazole atau PPI lainnya, pasien dengan sirosis hati, kehamilan atau menyusui, pasien yang
menderita kanker usus atau menerima atazanavirsulfate.
Pelajari Obat
Pasien yang memenuhi syarat menerima injeksi lansoprazole 30 mg dicampur dengan 0,9% NaCl atau larutan glukosa 5% dan diberikan oleh i.v.
teteskan dua kali sehari, atau injeksi lansoprazole 30 mg dicampur dengan 20mLof0.9% NaClor5% larutan glukosa dan diberikan dengan lambat i.v.
injeksi dua kali sehari, maksimal 7 hari.
Prosedur
Setibanya di UGD, anamnesis dan pemeriksaan fisik dilakukan, dan juga pengukuran kimia darah (hitung darah lengkap, SGPT, SGOT, kreatinin,
ureum). Untuk pasien yang secara hemodinamik stabil dengan tekanan darah normal, lansoprazole intravena diberikan dua kali sehari selama maksimal
7 hari atau sampai perdarahan berhenti dan pasien dapat menggunakan lansoprazole oral. Endoskopi GI bagian atas rutin dilakukan untuk
mengkonfirmasi penyebab pembalikan.

Jika UGIB tidak disebabkan oleh ulkus peptikum atau erosgastgastritis, pasien ini tidak termasuk dalam populasi efikasi, tetapi termasuk dalam
populasi yang aman. Pembibitan yang dihentikan tidak ada lagi hematemesis (cairan tabung hidung sudah jernih) dan / atau melena (tinja sudah tidak
hitam dan cair lagi) ). Tingkat hemoglobin dipantau setiap hari tergantung pada kondisi pasien. Tanda-tanda klinis dan kimia darah diukur lagi pada
hari terakhir terapi. Obat bersamaan dicatat, dengan indikasi masing-masing. Objektif dan tanda-tanda dan gejala subyektif yang muncul selama
pemberian lansoprazole intravena dicatat.
Efek samping serius (AE) dicatat: kematian, mengancam jiwa, memerlukan / memperpanjang rawat inap, mengakibatkan cacat / ketidakmampuan yang
persisten / signifikan, anomali / kelahiran bawaan, memerlukan intervensi untuk mencegah salah satu dari yang di atas atau dapat membuat pasien
terancam bahaya. . Semua kejadian buruk yang serius harus dilaporkan kepada sponsor dalam waktu 24 jam (1 hari kerja). Sebuah formulir khusus
dibuat dapat disediakan oleh penyelidik, dengan bantuan pemantauan dokter.
Analisis data
Analisis keamanan. Semua efek samping terdaftar, dan juga AE yang mungkin dan mungkin terkait dengan injeksi lansoprazole.
Analisis efikasi. Kemanjuran injeksi lansoprazole dievaluasi pada pasien UGIB karena tukak lambung atau gastritis erosif yang tidak memerlukan
endoskopi hemostasis. Pada pasien ini, efek hemostatik injeksi lansoprazole dievaluasi setiap hari sampai maksimum 7 hari perawatan dan persentase
pasien yang perdarahannya berhenti dihitung. Efek hemostatik ditentukan dan dinilai sebagai sangat baik, baik, adil atau buruk sebagai berikut. Luar
biasa: jika pemutusan berhenti dalam 3 hari. Baik: jika pendaratan berhenti dalam 5 hari. Adil: jika perdarahan berhenti dalam 7 hari. Buruk: jika
perdarahan tidak berhenti dalam 7 hari, atau pengobatannya berubah.

HASIL
Selama masa studi dari Desember2010 hingga Desember2011, pasien harus disaring, total
effectwasratedas“excellent”ifthebleedingstoppedwithin3days,and“good”ifthebleedingstoppedwithin5
days.Thus,theresultswere“excellent”in166patients(83.0%)and“good”in31patients(15.5%).Theseresults
werenotdifferentbetweenmalesandfemales,betweenagebelow60yearsand60yearsandabove,andbetween
baselineHbbelow10g/dLand10g/dLandabove.Conclusion:theresultsofthisobservationalpostmarketing
studyin200patientswithuppergastrointestinalbleedingduetopepticulcersorerosivegastritisdemonstrated
thatintravenouslansoprazoletwiceadaywaswelltoleratedandhighlyeffective.

Key words: postmarketing surveillance (PMS), lansoprazole, upper gastrointestinal bleeding (UGIB).

severe life-threatening disease with a mortality

INTRODUCTION rate that has remained constant at 5 to 10%, over
Upper gastrointestinal bleeding (UGIB) isa the past 50 years.1 Peptic ulcer is the most

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 Vol45•Number2•April2013 SafetyandefficacyofLansoprazoleinjectioninupperGIbleeding
common cause of UGIB, accounting for about
50% ofcases.2
Medical treatment of ulcer bleeding is
directed to keep the gastric pH above the
proteolytic range for pepsin.3 A rise of the pH
ofgastricjuiceto4almostcompletelyabolishes
the fibrinolytic activity in gastric juice. 4 In
keeping the gastric pH above the proteolytic
range for pepsin in bleeders, parenteral proton
pump inhibitors were demonstrated to be
more effective than parenteral histamine H2-
antagonists.3,5Lansoprazoleinjectionisthemost
recent intravenous PPI available in Indonesia.
Therefore, it requires a postmarketing study to
monitor its safety and effectiveness in clinical
practice.
Thegeneralobjectivewastoassessthesafety
and effectiveness of lansoprazole injection in
patientswithuppergastrointestinalbleeding,due
topepticulcersorerosivegastritis.Thespecific
objectives were: to assess safety based on the
objective and subjective signs and symptoms,
and abnormalities of liver function tests and to
assess effectiveness of its hemostaticeffect.
METHODS
Design and Patients
This was an observational, multicenter,
postmarketing study in patients with upper
gastrointestinal bleeding due to peptic ulcers
or erosive gastritis receiving intravenous
lansoprazole for a maximum of 7 days or until
the bleeding stopped and the patients were able
to take oral lansoprazole.
Patients recruited were those who came
to the emergency room (ER) of a hospital
with hematemesis and/or melena, and met the
followinginclusionandexclusioncriteria.Atotal
of200patientswereplannedtobeenrolledfrom
100 internal medicine specialists in Indonesia.
Patients with upper gastrointestinal bleeding
were considered eligible if they fulfilled the
following inclusion criteria: (i) Men or women
withuppergastrointestinalbleeding(UGIB)due
to peptic ulcers or erosive gastritis, (ii) aged 18
upto70yearsinclusive.Patientswereexcluded
from the study if they were hemodynamically
unstable (hypotension, tachycardy, or postural
changes in heart rate or blood
pressure),hypersensitive to lansoprazole or
other PPIs, patients with liver cirrhosis,
pregnancy or
lactation,patientssufferingfromgastrointestinal
cancer or receiving atazanavirsulfate.
Study Drug
Eligible patients received lansoprazole
injection 30 mg mixed with 0.9% NaCl or 5%
glucose solution and administered by i.v. drip
twice a day, or lansoprazole injection 30 mg
mixedwith20mLof0.9%NaClor5%glucose
solution and administered by slow i.v. injection
twice a day, for a maximum of 7days.
Procedure
Upon arrival at the ER, anamnesis and
physical examination were performed, and also
measurement of blood chemistry (complete
blood count, SGPT, SGOT, creatinine, ureum).
To patients who were hemodynamically stable
with normal blood pressure, intravenous
lansoprazole was given twice a day for a
maximum of 7 days or until the bleeding
stopped and the patients were able to take oral
lansoprazole. Routine upper GI endoscopy was
performedinordertoconfirmcauseofbleeding.
125
AriF. ActaMedIndones-

If the UGIB was not caused by peptic ulcers or patients evaluable for safety were 204, while
erosivegastritis,thesepatientswerenotincluded total patients evaluable for efficacy were 200
in the efficacy population, but included in the (4 patients did not meet the inclusion criteria:
safetypopulation.Thebleedingstoppedifthere 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 stoolwas 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 inTable2,medicalhistoryinTable3,andblood
patientcondition.Vitalsignsandbloodchemistry chemistry in Table4.
were measured again on the last day oftherapy.
Concomitantmedicationwasrecorded,withthe
respectiveindications.Objectiveandsubjective
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
birth, requires intervention to prevent one of
the above or may expose the patient to danger.
All serious adverse events had to be reported
Table 2. Vital signs
to the sponsor within 24 hours (1 working
Median
day).A Baseline Mean (SD) Missing
(Range)
specialformwasmadeavailabletobefilledinby SBP(mm Hg) 123.1(18.02) 120.0 (90–180) -
the investigator, with monitoring doctor’shelp. DBP(mmHg) 77.6(9.77) 80.0 (50–100) -
Data Analysis Heartrate
89.5(10.66) 88.0 (69–124) 1
(bpm)
Safety analysis. All adverse events were
Respiratory 20.0(3.02)
listed, and also AEs which were probably and rate (per min) 20.0 (14–31) 3

possibly related to lansoprazole injection. End of the

Efficacy analysis. Efficacy of lansoprazole study (day 7)
injection was evaluated in UGIB patients due SBP (mm Hg) 121.9 (12.89) 120.0 (90–190) 1
to peptic ulcers or erosive gastritis who did not DBP (mm Hg) 78.4 (7.46) 80.0 (60–100) 1

requireendoscopichemostasis.Inthesepatients, Heart rate

83.7 (8.01) 82.0 (68–124) 1
(bpm)
the hemostatic effect of lansoprazole injection Respiratory
was evaluated every day until a maximum of 7 rate (per min)
19.5(3.10) 20.0(14–36) 1

daysoftreatmentandthepercentageofpatients
whose bleeding stopped was calculated. The
hemostatic effect was determined and rated
as excellent, good, fair or poor as follows.
Excellent:ifthebleedingstoppedwithin3days.
Good:ifthebleedingstoppedwithin5days.Fair: if
the bleeding stopped within 7 days. Poor: if the
bleeding did not stop within 7 days, or the
treatment waschanged.
RESULTS
DuringthestudyfromDecember2010until
December2011,204patientswerescreened,total
Patients were mostly males (62.5%), mean
age was 52.1 years, and mean BMI was 23.0.
Systolic as well as diastolic blood pressure
did not change during the study.
Patient medical history consisted
ofgastrointestinaldiseasessuchaserosivegastriti
s (40.5%), gastric ulcer (26.5%), and duodenal
ulcer (12.0%), and the patients also suffered
from some comorbid diseases such as diabetes
mellitus, hypertension, coronary artery disease,
dyslipidemia, and others.

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 Vol45•Number2•April2013 SafetyandefficacyofLansoprazoleinjectioninupperGIbleeding

Laboratory findings
Table 3. Medical historyshowed that during treatment with lansoprazole injection, hemoglobin
level Gastrointestinal
increased. diseases:
At baseline, N hemoglobin % level was 9.9 g/dL and rose to 10.9
g/dLaftertreatmentwithlansoprazoleinjection.
- Erosive gastritis 81 Otherlaboratoryparameterswerealsoexamined
40.5 in this study.
During -one week
Gastric ulcerlansoprazole injection,
53 liver26.5
function tests (ALT and AST) did not change. Kidney
function, as shown
- Duodenal ulcer by creatinine and BUN,
24 were
12.0 improved (from an average of 37.9 to 35.4 mg/dL and
from a mean
- GERDof 1.2 to 1.1 mg/dL, respectively)
19 during treatment with lansoprazoleinjection.
9.5
Peptic ulcer was
- Hematemesis diagnosed endoscopically
13 in104patients(54%)anderosivegastritisin96
6.5
- Others: patients (46%).
- Dyspepsia 9 4.5 In this study, 92 patients were given
- Upper GI bleeding 3 1.5 lansoprazoleasintravenousdripand97patients as
- Others 6 3.0 intravenous slow injection, while 11 patients
Other diseases: were given a combination ofboth.
- Diabetes mellitus 11 5.5 Safety Analysis(n=204)
NoTable
-adverse events
Hypertension
4. Blood probably
chemistry parameteror possibly
15
before and afterrelated
7.5
the to lansoprazole injection was were reported
during study
the study. artery disease
- Coronary 5 2.5
- Dyslipidemia Before 2
After 1.0
Efficacy Variables
Analysis (n=200)
treatment treatment
p value
- Osteoarthritis 8 4.0
Hb (g/dL) 9.9 (2.68) 10.9 (1.82) < 0.001
Number and percentage of patients whose
- Rheumatoid arthritis 1 0.5
Creatinine UGIBstoppedduringtreatmentwithlansoprazole
- Obesity 1.2 (0.65) 2
1.1 (0.51) 1.0
0.01
(mg/dL) injection are shown in Figure 1. Hemostatic
- Others 20 10.0
BUN (mg/dL) 37.9 (17.22) 35.4 (14.19) < 0.001 effectsoflansoprazoleinjectionandhemostatic
ALT (U/L) 33.5 (19.92) 32.5 (14.49) 0.31 (NS) effects based on gender, age groups, and Hb
AST (U/L) 32.8 (28.64) 30.5 (10.78) 0.17 (NS) groups are shown in Table6.
Albumin (g/dL) 3.5 (0.50) 3.5 (0.49) 0.05

Figure 1. Percentage of patients whose bleeding stopped during the study

127
AriF. ActaMedIndones-

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
Excellent (bleeding associatedwithUGIBremained unchanged around 5-
stopped within 3 166 (83.0) 105 (84.0) 61 (81.3)
days)
10% forthepast50 years, despite
Good (bleeding
continuingimprovementin the diagnostic and
stopped within 5 31 (15.5) 19 (15.0) 12 (16.0) therapeutic modalities. Thisunchanged mortality
1

days)
rate may
Fair (bleeding
beaccountedbyageandprevalenceofconcurrentillness
stopped within 7 2 (1.0) 1 (1.0) 1 (1.3)
days) ,bothare important predictors of death,thatcontinue
Poor (bleeding toriseamongpatientswithUGIB.Patientswithbleedin
did not stopped 1 (0.5) - 1 (1.3) g usually die notfromexsanguination,
within 7 days)
butfromdecompensationduetootherdiseases.2Appro
Total 125 (100.0) 75 (100.0)
priate initial management is oneofthe
keysuccesstoreducemorbidityandmortality.In
general, causes of gastrointestinalbleedingwere
Thisstudyshowedthatlansoprazoleinjection varicealornon-variceal.Asystematicreviewand meta-
could stop bleeding in 10% of cases on day 1, analysis of 21 randomized controlledtrials comparing
and on day 3 the cumulative stopped bleeding 2915 patients (up toFebruary2003) showed that
rate was 83%, increasing to 99.5% after 7 days proton pumpinhibitortreatmentreduced rebleeding
of treatment. (OR=0.46;95%CI=0.33-
The hemostatic effects of lansoprazole 0.64)andtherequirementforsurgery(OR=0.59;
injection based on gender were not different 95%CI=0.46-0.76)afterulcerbleedingbutdidnot reduce
(Kolmogorov Smirnov test: Z = 0.183, p = 1.0). mortality(OR=1.11; 95%CI=0.79-
Based on age groups (<60 years and >60 years) 1.57).7Whittleetal.8haveshownthat,unlikeinthe skin
the hemostatic effects of lansoprazole injection or vasculature, platelet aggregationplaysa minimal
were also not different (Kolmogorov- Smirnov role in the initial hemostaticeventsinthe gastric
test: Z=0.594, p=0.87), neither the hemostatic mucosa and that the
effects of lansoprazole injection based on Hb arrestofgastrichemorrhageisbroughtaboutlargelybypr
groups at baseline (Kolmogorov- ocesses
Smirnov test: Z=0.521, p=0.95). primarily involving the coagulation system.
The s t r o n g e r d r u g s s u p p r e s s i n g
DISCUSSION acid production, the better in stopping the
In the present study, it was found that 104 gastrointestinalbleeding.Protonpumpinhibitors
cases (52%) of the 200 UGIB cases were due raise the pH to about 6.9 The target therapeutic
to peptic ulcer and 96 cases (48%) to erosive goal is to achieve an intragastric pH above 6,
gastritis. Many studies have shown that 50% of at which the clotting process is optimal and
the UGIB cases were caused by peptic ulcer. 2 any formed clot is stabilized. The success of
Research conducted at Cipto Mangunkusumo hemostasisishighlydependentontheintragastric
Hospital that analyzed patients who presented pHandstudieshaveshownthat,whentheintra-
with upper gastrointestinal bleeding, foundthat gastric pH is low, platelet function is impaired
and pepsinogen is activated to pepsin, which
disaggregates plateletplugs.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)

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Vol45•Number2•April2013 SafetyandefficacyofLansoprazoleinjectioninupperGIbleeding
Total 45 (100.0) 155 (100.0) 96 (100.0) 104 (100.0)

129
AriF.
A meta-analysis of 27 randomized trials of
H2-receptor antagonists in over 2500 patients
with acute UIGB suggested that the drugs
reduced the rates of rebleeding, surgery and
mortality,byabout10,20,and30%,respectively,
notably among those with gastric ulcers.12 In a
meta-analysiscomparingprotonpumpinhibitors
withH2antagonists,itwasfoundthatpersistent or
recurrent bleeding was less frequent with
proton pump inhibitors (6.7) than with H2
antagonists (13.4%) (OR 0.4; 95%CI: 0.27-
0.59). The need for surgery and mortality rates
didnotreachstatisticalsignificancebutshowed a
favorable trend towardsPPIs.5
Mucosal fibrinolytic activity is enhanced
in patients with bleeding gastrointestinal
ulcers.
Acidsuppressivetherapyreducedthisincreased
activity and ultimately decreased bleeding in
pepticulcers.13
This post-marketing survey showed that
lansoprazole injection could stop upper GI
bleeding in 10% of cases on day 1, and 83%
of the upper GI bleeding stopped on day 3,
increasing to 99.7% after 7 days of treatment.
This indicates that lansoprazole injectionworks
quickly to stop bleeding. The hemostatic effect
was rated as excellent if the bleeding stopped
within 3 days. Accordingly, this drug was
excellent for as much as 83%. These findings
suggest that lansoprazole may be useful in
situations where rapid acid control is required,
such as in emergency caresituations.
A preliminary study using intravenous
lansoprazole 30 mg bid in patients with UGIB
for 7 days showed that bleeding was arrestedin
16 of 18 patients (89%) within 3days.14
A previous study using oral omeprazole 40
mg bid vs. placebo in patients with bleeding
pepticulcersfor5daysshowedthatomeprazole
therapywasassociatedwithsignificantreductions
intheratesoffurtherbleeding(10.9%vs.36.4%)
andsurgicalintervention(7.2%vs.23.6%),and
the need for transfusion (29.1% vs. 70.9%). 15
Another study with bolus i.v. (80 mg) followed
by infusion (8 mg/h) of omeprazole vs.placebo
for 72 hours in severe ulcer hemorrhage after
endoscopic therapy showed that omeprazole
reduced the number of operations (5.4% vs.
11.1%),endoscopictreatments(4.6%vs.11.1%),
130
ActaMedIndones-
andthedurationandseverityofbleeding(18.0%
vs. 31.4% with moderate or severe bleeding). 16
Bolus i.v. (80 mg) followed by infusion (8
mg/h) of omeprazole for 3 days in patients
with bleeding peptic ulcers after endoscopic
treatment was also studied by Lau et al. 17 and
showed that omeprazole reduced the risk of
recurrent bleeding (6.7% vs. 22.5% within 30
days;HR=3.9).
A recent prospective study conducted by
Liangetal.18showedthathigh-dosepantoprazole
infusiontherapyfollowingendoscopichemostasis
treatmentisnotsuperiortolow-dosePPItherapy in
terms of reducing rebleeding among lowrisk
patients with a bleeding peptic ulcer (11.1% in
each group). A review by van Rensburg and
Cheerconcludesthatintravenouspantoprazoleis
aneffectiveoptioninthetreatmentofUGIB,the
preventionofrebleeding,andfortheprophylaxis
of acute bleeding stressulcers.19
Ameta-analysisof24randomizedcontrolled
trials (4373 participants) through November
2004 on the efficacy of PPIs for peptic ulcer
bleeding showed that treatment with PPIs did
notreducemortality(OR=1.01)butsignificantly
reduced rebleeding (OR=0.49; 95% CI=0.37-
0.65) and the need for surgery (OR=0.61;
95% CI=0.48-0.78). Treatment with PPIs
significantly reduced mortality in Asian trials
(OR=0.35; 95% CI=0.16-0.74) and in patients
with active bleeding or a nonbleeding visible
vessel (OR=0.53; 95% CI=0.31-0.91).20This
meta-analysiswastheextensionoftheprevious
one7, involving 50% more patients, giving the
sameresults.
In this survey, hemoglobin was also
evaluated. During treatment with lansoprazole
injection, hemoglobin level increased. At
baseline,hemoglobinlevelwas9.9g/dLandrose
to 10.9 g/dL after treatment with lansoprazole
injection. These data demonstrated that during
administration of lansoprazole, gastrointestinal
bleedingdidnotoccur,clinicallyaswellasinthe
laboratory. In several studies, low hemoglobin
value is one predictor ofrebleeding.21
Several laboratory parameters were also
examined in this study. The use of lansoprazole
injectionfor1weekdidnotaffectliverfunction.
Kidney function (creatinine and BUN)was
Vol45•Number2•April2013 SafetyandefficacyofLansoprazoleinjectioninupperGIbleeding
improved during treatment with lansoprazole
injection and these conditions were in line with
the cessation of gastrointestinal bleeding.
CONCLUSION
The res ults of this o bs e r va t i o na l
postmarketing study in 200 patients with
endoscopicallyconfirmeduppergastrointestinal
bleedingduetopepticulcersorerosivegastritis
demonstratedthatintravenouslansoprazoletwice a
day was well tolerated and highlyeffective.
The authors declare that they have no
conflictsofinterestinrelationtothismanuscript.
ACKNOWLEDGMENTS
We acknowledge PT. Takeda Indonesia for
funding this study. We also thank all
physicians who participated in this
postmarketing study.
CONFLICT OF INTEREST
The authors received grant support from
PT. Takeda Indonesia.
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