The document discusses potassium-competitive acid blockers (p-CABs) as innovative treatments for acid-related diseases, highlighting vonoprazan's advantages over traditional proton pump inhibitors (PPIs). It details vonoprazan's rapid onset, long duration, and effectiveness in treating conditions like erosive esophagitis and H. pylori eradication, while also acknowledging the limitations of existing PPI therapies. The document emphasizes the necessity for local clinical trials in Bangladesh to assess the drug's efficacy and safety in the regional population.

1. POTASSIUM-COMPETITIVE ACID BLOCKER:
A NEW ERA FOR THE TREATMENT OF ACID-RELATED DISEASES
DR.DEBPROSAD ADHIKARY
MD(GASTRO)
REGISTRAR( MEDICINE),SMCH

2. • Acid-related diseases (ARDs), such as PUD
and GERD represent a major health-care concern
• Major milestones during the last 50 years…
Discovery of H2-receptors and development of
H2RB
Identification of H+,K+-ATPase as the parietal
cell proton pump and development of PPIs and
Identification of H. pylori as the major cause of
PUD and development of effective eradication
regimens

4. Regulation of stomach acid secretion

5. Mechanism
of HCL
secretion

7. Mechanism of
action of PPI

11. • Although traditional PPI treatments have
been effective and successful, there are
limitations…
• Slow onset of action
• Short half-life
• Insufficient acid suppression

12. • Large variation in efficacy among patients due
to CYP2C19 polymorphism
• Unsatisfactory effects at night and
• Instability in acidic conditions

13. TO OVERCOME THESE…..
• Vonoprazan (TAK-438), a potassium-
competitive acid blocker (P-CAB), was
developed

14. HISTORY OF POTASSIUM-COMPETITIVE ACID BLOCKERS
(P-CABS)
• P-cabs are a group of drugs developed in early 1980s
• First drug developed was SCH28080 ,but stopped due to its toxic
effects on liver
• AZD 0865(Linaprazan),a reversible inhibitor of PP with rapid onset of
action
• In pase II and III trials showed similar efficacy to esomeprazole for
treating esophagitis
• Further trials could not be conducted as it was not superior to
esomeprazole and there was hepatotoxicity

15. • Revaprazan,first P-cabs used in clinical practice in South Korea
• Quick onset of action but was not superior to existing PPI
• Vonoprazan fumerate(TAK-438) second P-cab introduced in
clinical practice,marketed in Japan in early 2015s
• Became popular because of its superior properties such as
rapid onset of action,long duration of action,consistent and
potent acid suppression compared to traditional PPI

16. •Found to have satisfactory effects and a good
safety profile in clinical studies of…
•Gastric and duodenal ulcers
•Reflux esophagitis
•NSAID-associated ulcers and
•H. pylori eradication

17. •P-CABs inhibit PP in a reversible and K+-
competitive manner
•Exhibit almost complete inhibition of gastric
acid secretion from the first dose

18. FAST ACTING: FULL EFFECT FROM FIRST DOSE

19. PHARMACOKINETICS
• Vonoprazan is orally active P-cab accumulate within acid
secretory canaliculi
• Binds to tyr 799 of alpha subunit of PP to compete with
potassium binding and thus inhibits the function of the
pump
• Its effects are reversible and dose dependent
• Meal have no effect on rate of absorption,attains Cmax in
less than 2 hours.Plasma t1/2 is more than 6-9 hours for
vonoprazan

20. PROVEN SUPERIORITY OVER LANSOPRAZOLE
Of Healing of Erosive Esophagitis (EE)
Ref: Gastroenterology.
2023 Jan;164(1):61-
71 PMID: 36228734.
LPZ VPZ LPZ VPZ

21. PROVEN SUPERIORITY OVER LANSOPRAZOLE
Of Maintenance of Erosive Esophagitis (EE)
World J Gastroenterol.
2018 Apr
14;24(14):1550-1561
PMID: 29662293;
PMCID:
PMC5897859.
EE
recurrence
during
24
week
maintenance
period
VPZ 20mg VPZ 10mg LPZ 15mg

22. NOCTURNAL ACID BREAKTHROUGH (NAB)
Vonoprazan 20 mg
6.85
Rabeprazole 20 mg
0.6 – 1.4
Lansoprazole 30 mg
0.9 – 2.1
Esomeprazole 20 mg
1.3 – 1.6
• Vonoprazanhas the advantagesin Night Time Acid BreakthroughControl by having longer
half-life and sustained pharmacodynamic effect
Ther Adv Gastroenterol 2018, Vol.11: 1–14
Half Life of P-CAB vs PPIs

26. H.PYLORI ERADICATION
• On 2017, WHO listed H.pylori among 16 antibiotic-resistant
bacteria that pose the greatest threat to human health
• H. pylori infection can be eradicated by elevating intragastric
pH using an acid suppressant in combination with at least 2
antibiotics
• H. pylori enters the growth phase from a stationary phase at
intragastric pH above 5, at which point it becomes susceptible
to antibiotics

27. Results Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects
completed first-line therapy and 50 subjects completed second-line therapy. The first-line
eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with
vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being
16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of
vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high
(98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50).
Gut: first published as 10.1136/gutjnl-2015-311304 on 2 March 2016.

30. PREVENTION OF RECURRENCE OF LOW-DOSE
ASPIRIN/NSAIDS-RELATED ULCERS
• Risk factors associated with the
occurrence of NSAID-related
ulcers:
• History of GI ulcer with bleeding
• Concomitant use of two or more
NSAIDs/low-dose aspirin (LDA)
• High dose of NSAIDs
• Concomitant use of
anticoagulant agent
• History of gastric and duodenal
ulcers
• Age over 70 years
• H. pylori infection
NSAID use and H. pylori infection are independent and synergistic risk
factors for gastric and duodenal ulcers and bleeding

31. • NSAID associated upper GI injury is pH-dependent
• The higher the intragastric pH, the lower the incidence
of injury
• Vonoprazan strongly inhibits acid production from the
first dose
• Well tolerated when administered with LDA or NSAIDs

32. Gut: first published as 10.1136/gutjnl-2017-314010 on 7 October 2017.

33. Complications of long term PPI therapy

35. INDICATION AND DOSAGE
• Reflux oesophagitis
• Adult: 20 mg once daily for 4 weeks, may be followed
by a further 4 weeks if necessary
• Maintenance therapy -10 mg once daily, may be
increased to 20 mg once daily if needed
• Gastric ulcer
Adult: 20 mg once daily for 8 weeks

36. • Duodenal ulcer
• Adult: 20 mg once daily for 6 weeks
• Prophylaxis of NSAID-induced ulcers
• Adult: Including cases that occur during low-dose
aspirin therapy: 10 mg once daily
• Eradication of H. pylori associated with PUD
• Adult: 20 mg bid for 7 days in combination with
amoxicillin and clarithromycin

37. • A 2021 study found that dexlansoprazole, followed by lansoprazole,
had the strongest safety signal for both AKI and CKD
• Rabeprazole and omeprazole had the lowest signals for AKI and CKD,
respectively. This means they were the least likely to lead to these
types of kidney conditions

39. Characteristics PPI Vonoprazan
Maximum Inhibition of Acid Secretion After 5-7 doses From 1st dose
Onset of Action Slow Rapid
pH >4 holding time ratio Esomeprazole 20 mg: 61.2 % Vonoprazan 20 mg: 85.8%
Erosive Esophagitis (EE) Healing Rate (LA Grade C & D) Lansoprazole 30 mg: 72.0% Vonoprazan 20 mg: 91.7%
Erosive Esophagitis (EE) Healing Rate (All Patient) Lansoprazole 30 mg: 86.6% Vonoprazan 20 mg: 92.9%
Rate of EE Recurrence Lansoprazole 15 mg: 16.8% Vonoprazan 20 mg: 2.0%
H. Pylori Eradication Rate 76.4% 92.6%
Intra-Patient variability
(Influence of CYP2C19 polymorphism)
Yes No
Time of Dosing Before meal for optimum control Meal independent
Prodrug Yes No
Acid Stability Labile Stable
Acid Inhibition Irreversible Reversible
Half-Life 1-2 hours 6-9 hours
Need for Enteric-Coated Formulation Yes No
UNIQUE BENEFITS OVER PPIs

40. BANGLADESH PERSPECTIVE
• There is lack of comprehensive clinical trials conducted within
Bangladesh itself
• Most of the data available on Vonoprazan's efficacy and safety
come from other countries
• May not fully reflect the genetic and lifestyle variations of the
Bangladeshi population
• As a result, there is an urgent need for thorough and locally-
conducted trials to find out the drug's effectiveness and
potential side effects on the people of Bangladesh