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.

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

What is the most common condition associated with GERD?

A. B. C. D. E. Scleroderma Type 2 Diabetes Mellitus Pregnancy Peptic ulcer disease Hypertension

Which of the following usually raise the incidence of GERD?

A. B. C. D. E. F. Cigarette smoking Alcohol Calcium channel blockers Fatty foods Hearing this RTD before meal All of the above

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

Gastro Esophageal Reflux

Normal physiologic phenomenon Experienced intermittenly by most people Particularly after a meal

High amount of gastric juice

Refluxes into esophagus Symptoms appear +/- Esophageal mucosal injury (Esophagitis)

GERD

High Symptoms Prevalence

60%
50% 40% 30% 20% 10% 0% Daily Weekly Monthly
7.00% 20.00%
59.00%

Frequency of heartburn and/or regurgitation

Locke et al. Gastroenterology 1997;112:1148. Princeton, NJ. The Gallup Organization 1988.

Majority Dont Seek Medical Attention

The Need To Diagnose & Treat

Negative impact on health-related quality of life

Risk factor for esophageal adenocarcinoma

Pathophysiology
Simple Plumbing Circuit Esophagus: Antegrade pump LES: Valve Stomach: Reservoir

Hiatal Hernia

Gastric Contents Trapped in Hernial Sac

Clinical Presentation
Classic GERD Extraesophageal/Atypical GERD Complicated GERD

Classical Symptoms

Heartburn Regurgitation Dysphagia

Extraesophageal Manifestations
Pulmonary Asthma Aspiration pneumonia Chronic bronchitis Pulmonary fibrosis Other Chest pain Dental erosion ENT Hoarseness Laryngitis Pharyngitis Chronic cough Globus sensation Dysphonia Sinusitis Subglottic stenosis Laryngeal cancer

Extraesophageal Pathophysiology

Complicated Symptoms
Dysphagia: Difficulty swallowing Food sticks or hangs up Odynophagia Retrosternal 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 Effectiveness
Treatment
Lifestyle modifications/antacids

Response
20%

H2-receptor antagonists
Single-dose PPI Increased-dose PPI

50%
80% 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 meals Avoid 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

Barretts esophagus
Adenocarcinoma

When To Do Surgery?
Intractable GERD Rare Difficult to manage strictures Severe bleeding from esophagitis Non-healing ulcers Requiring long-term PPI-BID in a healthy young patient Persistent regurgitation/aspiration symptoms Not Barretts esophagus alone

With Rabeprazole 20mg Once Daily...

DAY 1 Day-time & Night-time symptoms Significantly Decreased

Open Label, Multicentre, 8 weeks study in 2499 patients Patient with satisfactory Day-time or Night-time Symptom Relief

80%

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

With Rabeprazole 20mg Once Daily...

DAY 1 Faster symptoms relieve in SEVERE & VERY SEVERE heartburn 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

Holtman G, et al. A randomized, double-blind, comparative study of standard-dose rabeprazole and highdose omeprazole in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2002; 16: 479-485

With Rabeprazole 20mg Once Daily...

WEEK 4 High rates of esophageal lesions healing

A randomized, double-blind study for 8 weeks (n=230) in patients with GERD; sub analysis of Grade III population (n=45)

*p = ns **p = ns
Holtman G, et al. A randomized, double-blind, comparative study of standard-dose rabeprazole and highdose omeprazole in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2002; 16: 479-485

With Rabeprazole 20mg Once Daily...

Effective in treating symptoms when others failed Patient with complete symptom relief

Of the total study population, a subset (n=502) reported ineffective relief with prior use of either Lansoprazole or Omeprazole

Complete heartburn relief: >50% On day 1 > 80% On day 28

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

With Rabeprazole 20mg Once Daily...

DAY 1 The most potent acid inhibitor of all the PPI

Median 24-hour pH monitoring in a Crossover Study A Cross-Over, Double Blind, Randomized Study of H. Pylorinegative subjects (n=18). Result of post-dose (08.30-08.00 h)

*p < 0.03

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

With Rabeprazole 20mg Once Daily...

Single Dose More effective than esomeprazole in increasing intragastric pH & maintaining optimal pH (>3 for Ulcer & >4 for GERD)

Open, Randomised, 2-way crossover, Clinical pharmacology study in H. Pylori-negative healthy volunteers n=24: 14-24 hours post-dose (Sub-analysis during night-time period)

*p < 0.05 Warrington S, et al. Effects of single doses of rabeprazole 20mg and esomeprazole 40mg on 24h intragastric pH in healthy subjects. Eur J Pharmacol 2006; 62: 685-691

With Rabeprazole 20mg Once Daily...

DAY 1 Produced greater acid suppresion than IV pantoprazole 40 mg

A randomized, Double-Blind, Double-Dummy, 2-way crossover study of H. Pylorinegative volunteers (n=33). 95% confidence intervals are represented by vertical lines

Complete 24-Hour recording

*p < 0.05 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

Rabeprazole has the fastest onset of action compared with other PPIs

Every PPI requires acidic environment to be converted into their active forms Rabeprazole remains activated rapidly even in high pH
Chemical Activation Half-Life

pH: 1.2

pH: 5.1

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

With Rabeprazole 20mg Once Daily...

Higher number of NERD patients reporting satisfactory relief from heartburn & regurgitation Number of symptom free patients

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

Lebih mudah dan nyaman dengan Pariet

Ditoleransi dengan baik

Ukuran tablet lebih kecil Dapat diminum sebelum dan sesudah makan

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

Sediaan Pariet 10mg Pariet 20mg Prosogan 30mg Nexium 20mg Nexium 40mg Pantozol 20mg Pantozol 40 mg OMZ 20mg Lancid 30mg Pumpitor 20mg

Harga per tablet (HNA) 12,292 14,216 14,321 12,227 14,927 11,100 13,900 11,000 10,750 10,560

Biaya PPI untuk pengobatan 417,928 483,344 801,990 684,720 835,920 621,600 778,400 616,000 602,000 591,360

Index

Selisih Biaya 65,416 384,062 266,792 417,992 203,672 360,472 198,072 184,072 173,432

16% 92% 64% 100% 49% 86% 47% 44% 41%

Faster recovery Only 7 days!

The one & only approved 7-day treatment for H. pylori infections
Times needed for H. pylori eradication using combination therapy

Chey WD, Wong BCY. American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection. Am J Gastroenterol 2007;102:18081825

Sediaan

Harga per tablet (HNA) 14,216 14,321 14,927 19,782 11,000 10,750 10,560

Biaya PPI untuk pengobatan 99,512 200,498 149,271 197,820 110,000 150,500 105,600

Index

Selisih Biaya

Pariet 20mg Prosogan 30mg Nexium 40mg Losec 20mg OMZ 20mg Lancid 30mg Pumpitor 20mg

101% 100,986 50% 99% 11% 51% 6% 49,759 98,308 10,488 50,988 6,088

Interaksi obat antara PPI dengan obat-obatan yang berhubungan dengan penghambatan cytochrome P450
1-8

Rabeprazole

Pantoprazole

Warfarin

Omeprazole

Warfarin

Phenytoin

Diazepam

Disulfiram

Lansoprazole

Warfarin

Phenytoin

Diazepam

Digoxin

Theophylline

Tacrolimus

Esomeprazole

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

Rabeprazole for Elderly

1. Clinically effective 2. No dosage adjustment & well tolerated in mild to moderate impairment in renal or liver function

Whitaker M. Eur J Gastroenterol Hepatol 2002; 14 (Suppl 1): S5 - 9

Serum gastrin level on Rabeprazole for more than 5 years

Caos A et al. Aliment Pharmacol Ther 2005; 22 (3): 193 - 202