ORIGINAL ARTICLE
Safety and Efficacy of Lansoprazole Injection in Upper Gastrointestinal Bleeding: a Postmarketing Surveillance Conducted in Indonesia Ari F. Syam1, Arini Setiawati2,3 Department of Internal Medicine, Faculty of Medicine, University of Indonesia-Cipto Mangunkusumo Hospital, Jakarta, Indonesia. 2 Clinical Study Unit, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia. 3 Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia. 1
Correspondence mail: Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia-Cipto Mangunkusumo Hospital. Jl. Diponegoro no. 71, Jakarta 10430, Indonesia. email:
[email protected].
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 Acta Medica Indonesiana - The Indonesian Journal of Internal Medicine
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Ari F. Syam
Acta Med Indones-Indones J Intern Med
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). INTRODUCTION
Upper gastrointestinal bleeding (UGIB) is a severe life-threatening disease with a mortality rate that has remained constant at 5 to 10%, over the past 50 years.1 Peptic ulcer is the most common cause of UGIB, accounting for about 50% of cases.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 of gastric juice to 4 almost completely abolishes 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 H2antagonists.3,5 Lansoprazole injection is the most recent intravenous PPI available in Indonesia. Therefore, it requires a postmarketing study to monitor its safety and effectiveness in clinical practice. The general objective was to assess the safety and effectiveness of lansoprazole injection in patients with upper gastrointestinal bleeding, due to peptic ulcers or erosive gastritis. The specific 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 hemostatic effect. 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.
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Patients recruited were those who came to the emergency room (ER) of a hospital with hematemesis and/or melena, and met the following inclusion and exclusion criteria. A total of 200 patients were planned to be enrolled from 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 with upper gastrointestinal bleeding (UGIB) due to peptic ulcers or erosive gastritis, (ii) aged 18 up to 70 years inclusive. Patients were excluded 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, patients suffering from gastrointestinal cancer or receiving atazanavir sulfate. 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 mixed with 20 mL of 0.9% NaCl or 5% glucose solution and administered by slow i.v. injection twice a day, for a maximum of 7 days. 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 performed in order to confirm cause of bleeding.
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 erosive gastritis, these patients were not included in the efficacy population, but included in the safety population. The bleeding stopped if there was no more hematemesis (the nasal tube fluid was already clear) and/or melena (the stool was not black and liquid anymore). Hemoglobin level was monitored daily depending on the patient condition. Vital signs and blood chemistry were measured again on the last day of therapy. Concomitant medication was recorded, with the respective indications. Objective and subjective signs and symptoms which emerged during intravenous lansoprazole administration were recorded. Serious adverse events (AE) were noted: death, life-threatening, requires/prolongs hospitalization, results in persistent/significant disability/incapacity, a congenital anomaly/ birth, requires intervention to prevent one of the above or may expose the patient to danger. All serious adverse events had to be reported to the sponsor within 24 hours (1 working day). A special form was made available to be filled in by the investigator, with monitoring doctor’s help. Data Analysis
Safety analysis. All adverse events were listed, and also AEs which were probably and possibly related to lansoprazole injection. Efficacy analysis. Efficacy of lansoprazole injection was evaluated in UGIB patients due to peptic ulcers or erosive gastritis who did not require endoscopic hemostasis. In these patients, the hemostatic effect of lansoprazole injection was evaluated every day until a maximum of 7 days of treatment and the percentage of patients whose bleeding stopped was calculated. The hemostatic effect was determined and rated as excellent, good, fair or poor as follows. Excellent: if the bleeding stopped within 3 days. Good: if the bleeding stopped within 5 days. Fair: if the bleeding stopped within 7 days. Poor: if the bleeding did not stop within 7 days, or the treatment was changed. RESULTS
During the study from December 2010 until December 2011, 204 patients were screened, total
patients evaluable for safety were 204, while total patients evaluable for efficacy were 200 (4 patients did not meet the inclusion criteria: 3 patients aged
