Download - GERD
GERD Role of Rabeprazole
Sutanto Tanaka, MDOctober 13, 2012
Which of the following statements is true?
A. GERD is one of the least common conditions affecting the GI system.
B. All GERD patients will require medication to control their symptoms.
C. + 50% of adults experience reflux at least once a month.
D. GERD symptoms generally occur before meals.
October 13, 2012
Regarding the symptoms of GERD, which one is false?
A. Heartburn is a common manifestation of GERD
B. Dysphagia is associated with GERD and esophageal cancer
C. Symptoms of GERD are usually worse with lying down
D. A glass of wine can frequently help with the symptoms of GERD
October 13, 2012
What is the most common condition associated with
GERD?
A. Scleroderma
B. Type 2 Diabetes Mellitus
C. Pregnancy
D. Peptic ulcer disease
E. Hypertension
October 13, 2012
Which of the following usually raise the incidence of GERD?
A. Cigarette smoking
B. Alcohol
C. Calcium channel blockers
D. Fatty foods
E. Hearing this RTD before meal
F. All of the above
October 13, 2012
When should a patient consider surgery for GERD?
A. Symptoms are unresolved with maximum medical therapy.
B. GERD is complicated by hiatus hernia and continues to interfere with quality of life.
C. Does not desire or is unable to take any more medications.
D. All of the above
October 13, 2012
Gastro Esophageal Reflux
Normal physiologic phenomenon Experienced intermittenly by most
people Particularly after a meal
GERD
High amount of gastric juice
Refluxes into esophagus
Symptoms appear
+/- Esophageal mucosal injury (Esophagitis)
Locke et al. Gastroenterology 1997;112:1148.Princeton, NJ. The Gallup Organization 1988.
High Symptoms Prevalence
Daily Weekly Monthly0%
10%
20%
30%
40%
50%
60%
7.00%
20.00%
59.00%
Frequency of heartburn and/or regurgitation
Majority Don’t Seek Medical Attention
The Need To Diagnose & Treat Negative impact on health-related quality of
life Risk factor for esophageal adenocarcinoma
Pathophysiology
Simple Plumbing CircuitEsophagus: Antegrade pumpLES: ValveStomach: Reservoir
Hiatal Hernia
LES: Low Pressure
Diaphragmatic Crura External Sphincter Dysfunction
Gastric Contents Trapped in Hernial Sac
Clinical Presentation
Classic GERDExtraesophageal/Atypical GERDComplicated GERD
Classical Symptoms
Heartburn – Regurgitation – Dysphagia
Extraesophageal Manifestations
PulmonaryAsthmaAspiration pneumoniaChronic bronchitisPulmonary fibrosis
OtherChest painDental erosion
ENTHoarsenessLaryngitisPharyngitisChronic coughGlobus sensationDysphoniaSinusitisSubglottic stenosisLaryngeal cancer
Extraesophageal Pathophysiology
Complicated Symptoms
Dysphagia:Difficulty swallowingFood sticks or hangs up
OdynophagiaRetrosternal pain with swallowing
Bleeding
ALARM SYMPTOMS!!!• Systemic signs:
Fevers/Chills/Nightsweats• Weight loss• Abdominal pain• Upper/Lower GI Bleeding• Syncope• Shortness of Breath/Chest Pain• Dysphagia• Hoarseness
Start Treating? Do Workups?
Heartburn – Regurgitation – Dysphagia
CLASSIC!!!START TREATMENT! (70% CORRECT)
When To Do Additional Tests?
• Uncertain diagnosis: Atypical symptoms
• Symptoms associated with complications
• Inadequate response to therapy• Recurrent symptoms• Prior to anti-reflux surgery
Diagnostic Tests
• Barium esophagogram • Esophagogastroduodenoscopy• Esophageal manometry• Ambulatory 24-hour pH
monitoring
Treatment Goals
• Eliminate symptoms• Heal esophagitis• Manage or prevent complications• Maintain remission
Treatment EffectivenessTreatment Response
Lifestyle modifications/antacids 20%
H2-receptor antagonists 50%
Single-dose PPI 80%
Increased-dose PPI Up to 100%
Lifestyle Modifications Elevate head of bed 4-6 inches Avoid eating within 2-3 hours of
bedtime Lose weight if overweight Stop smoking Modify diet
Frequent but smaller mealsAvoid fatty/fried food, peppermint, chocolate, alcohol, carbonated beverages, coffee & tea
OTC medications prn
GERD Chronic Relapsing Condition
• Esophagitis relapses quickly after cessation of therapy
> 50 % relapse within 2 months> 80 % relapse within 6 months
• Effective maintenance therapy is imperative
Complications
Erosive/ulcerative esophagitis
Esophageal stricture
Barrett’s esophagus
Adenocarcinoma
When To Do Surgery?
Intractable GERD RareDifficult to manage stricturesSevere bleeding from esophagitisNon-healing ulcers
Requiring long-term PPI-BID in a healthy young patient
Persistent regurgitation/aspiration symptoms
Not Barrett’s esophagus alone
Treatment FlowCharts
With Rabeprazole 20mg Once Daily...
Open – Label, Multicentre, 8 – weeks study in 2499 patients
Robinson M, et al. Onset of symptom relief with rabeprazole: a community-based, open-label assessment of patients with erosive oesophagitis. Aliment Pharmacol Ther 2002; 16: 445-454
≈ 80%
Patient with satisfactory Day-time or Night-time Symptom Relief
Day-time & Night-time symptoms Significantly DecreasedDAY 1
With Rabeprazole 20mg Once Daily...
A randomized, double blind & comparative study
Post hoc statistical analysis of the proportion of reports of severe heartburn in the first 3 days of treatment
Faster symptoms relieve in SEVERE & VERY SEVERE heartburnDAY 1
Holtman G, et al. A randomized, double-blind, comparative study of standard-dose rabeprazole and high-dose omeprazole in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2002; 16: 479-485
With Rabeprazole 20mg Once Daily...
A randomized, double-blind study for 8 weeks (n=230) in patients with GERD; sub analysis of Grade III population (n=45)
High rates of esophageal lesions healingWEEK 4
Holtman G, et al. A randomized, double-blind, comparative study of standard-dose rabeprazole and high-dose omeprazole in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2002; 16: 479-485
*p = ns**p = ns
With Rabeprazole 20mg Once Daily...
Of the total study population, a subset (n=502) reported ineffective relief with prior
use of either Lansoprazole or Omeprazole
Robinson M, et al. Onset of symptom relief with rabeprazole: a community-based, open-label assessment of patients with erosive oesophagitis. Aliment Pharmacol Ther 2002; 16: 445-454
Patient with complete symptom relief
Effective in treating symptoms when others failed
Complete heartburn relief:>50% On day 1
> 80% On day 28
With Rabeprazole 20mg Once Daily...
Median 24-hour pH monitoring in a Crossover Study
Pantoflickova D, et al. Acid inhibition on the first day of dosing: comparison of four proton pump inhibitors. Aliment Pharmacol Ther 2003; 17: 1507-1514
A Cross-Over, Double Blind, Randomized Study of H. Pylori-negative subjects (n=18). Result of post-dose (08.30-08.00 h)
The most potent acid inhibitor of all the PPI
DAY 1
*p < 0.03
With Rabeprazole 20mg Once Daily...
Open, Randomised, 2-way crossover, Clinical pharmacology study in H. Pylori-negative healthy volunteers
Warrington S, et al. Effects of single doses of rabeprazole 20mg and esomeprazole 40mg on 24-h intragastric pH in healthy subjects. Eur J Pharmacol 2006; 62: 685-691
n=24: 14-24 hours post-dose (Sub-analysis during night-time period)
More effective than esomeprazole in increasing intragastric pH & maintaining optimal pH (>3 for Ulcer & >4 for GERD)
SingleDose
*p < 0.05
With Rabeprazole 20mg Once Daily...
A randomized, Double-Blind, Double-Dummy, 2-way crossover study of H. Pylori-negative volunteers (n=33). 95% confidence intervals are represented by vertical lines
Armstrong D, et al. Oral rabeprazole vs intravenous pantoprazole: a comparison the effect on intragastric pH in healthy subjects. Aliment Pharmacol Ther 2006; 25: 185-196
Complete 24-Hour recording
Produced greater acid suppresion than IV pantoprazole 40 mgDAY 1
*p < 0.05
1. Pantoflickova D, et al. Acid inhibition on the first day of dosing: comparison of four proton pump inhibitors. Aliment Pharmacol Ther 2003; 17: 1507-1514
2. Kromer W et al. Differences in pH-Dependent Activation Rates of Substituted Benzimidazoles and Biological in vitro Correlates. Pharmacology 1998; 56: 57-70
Rabeprazole has the fastest onset of action compared with other PPIsEvery PPI requires acidic environment to be converted
into their active formsRabeprazole remains activated rapidly even in high pHChemical Activation Half-Life
pH: 1.2 pH: 5.1
With Rabeprazole 20mg Once Daily...
Fock KM, et al. Rabeprazole vs esomeprazole in non-erosive gastro-esophageal reflux disease: A randomized, double-blind study in urban Asia. World J Gastroenterol 2005; 11(20): 3091-3098
Number of symptom free patients
Higher number of NERD patients reporting satisfactory relief from heartburn & regurgitation
Lebih mudah dan nyaman dengan Pariet
Dapat diminum sebelum dan sesudah makan
Ditoleransi dengan baik
Ukuran tablet lebih kecil
Pengobatan awal cukup 4 minggu On – Demand therapy
1. Bour B, et al. On-demand maintenance therapy with rabeprazole (RAB) 10mg an effective alternative to continous therapy for patients with frequent gastroesophageal reflux symptomatic relapse. Gastroenterology 2003; 124(4(suppl 1)): A 219 – S 161
2. Bytzer P, et al. Six-month trial of on-demand rabeprazole 10mg maintains symptom relief in patients with non-erosive reflux disease. Aliment Pharmacol Ther 2004; 20: 181-188
SediaanHarga per tablet
(HNA)Biaya PPI untuk
pengobatanIndex
Selisih Biaya
Pariet 10mg 12,292 417,928 Pariet 20mg 14,216 483,344 16% 65,416 Prosogan 30mg 14,321 801,990 92% 384,062 Nexium 20mg 12,227 684,720 64% 266,792 Nexium 40mg 14,927 835,920 100% 417,992 Pantozol 20mg 11,100 621,600 49% 203,672 Pantozol 40 mg 13,900 778,400 86% 360,472 OMZ 20mg 11,000 616,000 47% 198,072 Lancid 30mg 10,750 602,000 44% 184,072 Pumpitor 20mg 10,560 591,360 41% 173,432
Biaya
Lebih H
emat
The one & only approved 7-day treatment for H. pylori infections
Faster recovery Only 7 days!
Chey WD, Wong BCY. American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection. Am J Gastroenterol 2007;102:1808–1825
Times needed for H. pylori eradication using combination therapy
SediaanHarga per tablet
(HNA)Biaya PPI untuk
pengobatanIndex
Selisih Biaya
Pariet 20mg 14,216 99,512
Prosogan 30mg 14,321 200,498 101% 100,986
Nexium 40mg 14,927 149,271 50% 49,759
Losec 20mg 19,782 197,820 99% 98,308
OMZ 20mg 11,000 110,000 11% 10,488
Lancid 30mg 10,750 150,500 51% 50,988
Pumpitor 20mg 10,560 105,600 6% 6,088
Biaya
Lebih H
emat
Interaksi obat antara PPI dengan obat-obatan yang berhubungan
dengan penghambatan cytochrome P450Rabeprazole
Pantoprazole
Omeprazole
Lansoprazole
Esomeprazole
Warfarin
Warfarin Phenytoin Diazepam Disulfiram
Warfarin Phenytoin Diazepam Digoxin Theophylline Tacrolimus
Warfarin Phenytoin Diazepam Citalopram Clomipramin Imipramin
1. Robinson M, et al. Drugs 2003;63:2739-54. 2. Ishizaki T et al. Aliment Pharmacol Ther 1999;13(Suppl.3):27-36. 3. Fuhr U, et al. Pharmazie 57(2002)9. 4. Giannini EG, et al. Dig Dis Sci 2006;51:1602-6. 5. Takahashi K, et al. Drug Metab Pharmacokinet 2007;22:441-4. 6. Hosohata K, et al. Drug Metab Pharmacokinet 2008;23:134-8. 7. Lim PWY, et al. Journal of Gastroenterology and Hepatology (2005)20:522-28. 8. Pariet SmPC 2008 Losec SmPC, Pantozol SmPC, Prosogan FD SmPC. Nexium SmPC 2008
1-8
Whitaker M. Eur J Gastroenterol Hepatol 2002; 14 (Suppl 1): S5 - 9
1. Clinically effective2. No dosage adjustment & well tolerated in
mild to moderate impairment in renal or liver function
Rabeprazole for Elderly
Serum gastrin level on Rabeprazole for more than 5 years
Caos A et al. Aliment Pharmacol Ther 2005; 22 (3): 193 - 202
THANK YOUOctober 13, 2012