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