Vonoprazan: A New Potassium-Competitive Acid Blocker

Abstract

Objective: To review the safety, efficacy, and tolerability of vonoprazan for the treatment of Helicobacter pylori infection in adults. Data Sources: A literature search was performed through PubMed using the following key terms: vonoprazan, Voquezna, TAK-438, potassium-competitive acid blocker, H pylori, and gastrointestinal. Study Selection and Data Extraction: Selected articles included those which described clinical studies of the pharmacology, pharmacokinetics, efficacy, safety, or tolerability of vonoprazan. Data Synthesis: Vonoprazan works by competing with potassium on the proton pump to inhibit gastric acid secretion. Phase 3 clinical trials have shown that vonoprazan is noninferior to proton pump inhibitors (PPIs) as a component of H pylori eradication regimens. Vonoprazan has also shown promise in duodenal ulcer-healing rates and in reducing symptoms of heartburn. Common adverse effects associated with vonoprazan include nasopharyngitis, diarrhea, constipation, flatulence, dyspepsia, headache, and abdominal pain. Conclusion: Clinical practice guidelines recommend PPIs as the antisecretory agent of choice in H pylori eradication regimens with histamine-2 receptor antagonists (H2RAs) as potential alternatives. However, the use of either class of medications may be limited by adverse effects, drug interactions, and tolerability. Potassium-competitive acid blockers (P-CABs), like vonoprazan, may be safe and effective alternative antisecretory agents for H pylori eradication regimens, as well as other gastrointestinal disorders.

Introduction

H pylori is a bacterium found in the gastric mucosal layer of approximately 60% of the population. It is implicated in causing 90% of duodenal ulcers (DUs) and a contributing factor to gastric ulcers (GUs). Not all patients who are infected with H pylori develop symptoms; nonetheless, it should be eradicated as its presence can increase the risk of developing gastric cancer. ¹ The method by which patients acquire H pylori is unknown; however, it is believed to be transmitted via the fecal-oral or oral-oral route. ² The risk of infection appears to be higher in individuals with low socioeconomic statuses, multiple siblings, or a parent who is also infected. When compared to non-Hispanic white patients, infection rates are higher in African Americans, Hispanic Americans, Native Americans, and Alaska Natives. ³

Current guidelines recommend several first-line treatments for eradicating H pylori in the United States (see Table 1). In each of these regimens, a proton pump inhibitor (PPI) is recommended as the antisecretory agent of choice due to superior efficacy in reducing acid secretion. ³ Although the risks associated with PPIs (increased risk of certain infections, bone loss, deficiencies in magnesium, as well as vitamin B12) tend to be related to long-term use, it is prudent for providers to be cautious about these risks. H2RAs approved for acid suppression may be considered as an alternative to PPIs, drug interactions (cimetidine) and the need for adjusting doses in elderly patients or renal dysfunction can limit their use.

Table 1.

First-Line Treatment Regimens for H pylori Eradication in the United States. ³

Regimen	Medication components	Duration	Approximate eradication rates, %
Clarithromycin triple therapy	Clarithromycin + amoxicillin OR metronidazole + PPI	14 days	80
Bismuth quadruple therapy	Bismuth + tetracycline + nitroimidazole + PPI	10-14 days	90
Concomitant therapy	Clarithromycin + amoxicillin + nitroimidazole + PPI	10-14 days	85
Sequential therapy	Amoxicillin + PPI for 5-7 days THEN clarithromycin + nitroimidazole + PPI for 5-7 days	10-14 days	85
Hybrid therapy	Amoxicillin + PPI for 7 days THEN amoxicillin + clarithromycin + nitroimidazole + PPI for 7 days	14 days	85
Levofloxacin triple therapy	Levofloxacin + amoxicillin + PPI	10-14 days	80
Fluoroquinolone sequential therapy	Amoxicillin + PPI for 5-7 days THEN fluoroquinolone + nitroimidazole + PPI for 5-7 days	10-14 days	85

Abbreviation: PPI, proton pump inhibitor.

This class of medications, P-CABs, inhibit acid secretion by competing with potassium on the proton pump. ⁴ Unlike PPIs, P-CABs bind reversibly to the receptor, are acid-stable, and are not affected by the presence of food. The purpose of this review is to discuss vonoprazan, the first P-CAB approved by the US Food and Drug Administration (FDA) in May 2022 as the combination packs Voquezna Dual Pak (vonoprazan and amoxicillin) and Voquezna Triple Pak (vonoprazan, amoxicillin, and clarithromycin) for the treatment of H pylori infection in adults. ⁴

Data Selection

A literature search was performed via PubMed from January 2010 to December 2022 using the search terms vonoprazan, Voquezna, TAK-438, potassium-competitive acid blocker, H pylori, and gastrointestinal. All relevant English-language studies assessing the pharmacokinetics, pharmacology, efficacy, safety, or tolerability of vonoprazan were evaluated. Information was also obtained from the FDA-approved package insert. References from previously published manuscripts were also examined to identify additional sources.

Pharmacology

Following food consumption, parietal cell receptors actively transport hydrogen ions across the canalicular membrane which are exchanged for luminal potassium ions. Hydrogen potassium adenosine triphosphatase (HK-ATPase) transfers equal amounts of hydrogen and potassium along with passive movement of chloride ions to promote an acidic gastric environment as well as maintain electrochemical neutrality across the membrane. The final step in gastric acid production is through the HK-ATPase, which is commonly referred to as a proton pump. ⁵

Both vonoprazan and PPIs block this final step in acid production. However, PPIs work through irreversible covalent binding to the alpha subunit of HK-ATPase whereas vonoprazan selectively and reversibly competes with luminal potassium ions required for hydrogen exchange.^4,5 The positively charged side chain enables strong hydrogen bonding and charge interaction with the potassium-binding site. Vonoprazan competes with potassium’s binding site to prevent potassium from binding and thereby inhibiting gastric acid secretion.^6,7

Hepatotoxicity, a problem with other P-CABs which are no longer available, is less of a concern with vonoprazan due to the absence of an imidazopyridine ring in its chemical structure. ⁸ Furthermore, due to the relatively high pKa value of vonoprazan (9.06), it does not require an acidic environment to bind to the enzyme and accumulates in gastric parietal cells to achieve longer-lasting gastric acid suppression. Unlike the PPIs, vonoprazan is acid stable and does not require an acidic environment for activation nor does it require enteric coating to protect from gastric degradation.^6,7

Pharmacokinetics

Vonoprazan is rapidly absorbed with peak plasma concentration (C_max) of 37.8 ng/mL being reached after 2 hours with a single dose and an average of 3 hours after reaching steady state with repeated dosing (t_max). The area under the curve (AUC) from administration to the end of the 12-hour dosing interval is 273 ng*hr/mL. ⁴ Both AUC and C_max increase dose proportionally with drug accumulation complete by the third day of treatment and little to no accumulation in plasma after repeated doses.^8,9 Meals high in fat have been shown to increase C_max by 5%, AUC by 15%, and t_max to 5 hours; however, these differences are not considered clinically significant. Thus, vonoprazan can be administered regardless of food intake. The half-life (t_1/2) is 7 to 9 hours regardless of a meal. ⁴ Vonoprazan displays time-independent pharmacokinetics with steady state being reached by day 3 or 4. ⁸ The volume of distribution (V_d) is 782.7 L with plasma protein binding of 85% to 88% and unlikely to be saturated even at drug concentrations above therapeutic range.^4,10 As previously stated, it has a relatively high pKa (9.06) resulting in near instant protonation and accumulation in gastric parietal cells within an acidic environment providing an explanation for its rapid onset, long-lasting duration of action (24 hours following a single dose and with repeated steady-state dosing), and elevated intragastric pH following drug discontinuation (~24 to 48 hours after the last dose).^4,11,12 When compared to the acid-reducing capabilities of a PPI, one study comparing vonoprazan to lansoprazole showed that the proportion of a 24-hour period with intragastric pH > 4 was 3-fold higher in the vonoprazan group after a single dose and 2-fold higher after 1 week. ¹³

Vonoprazan is metabolized via cytochrome P450 (CYP) through CYP3A4/5, CYP2B6, CYP2C19, CYP2C9, and CYP2D6 with none of its metabolites being pharmacologically active. It has also been shown to inhibit p-glycoprotein (p-gp); however, unlikely to have any clinically significant impact on p-gp inhibition.^10,14,15 In regards to CYP2C19 polymorphisms, there have been no confirmed differences in the pharmacokinetics of vonoprazan based on metabolizer status.^9,10 Vonoprazan is predominantly excreted via the urinary tract (67%), whereas, 31% is excreted in feces. Both routes have a minimal amount of unchanged drug at approximately 8% and 1.4%, respectively. ⁴

Clinical Trials (for Full Results See Table 2)

Table 2.

Detailed Results of Phase 3 Clinical Trials With Vonoprazan.^16-22

Author	Study design	Duration	Population size (n)	Comparator	Primary endpoint(s)	Results
Hou et al 16	DB, DD, PG	6 weeks	533	VON 20 mg, LAN 30 mg	DU healing rates	VON 96.9%, LAN 96.5%; DIFF 0.4% [95% CI: −3.00 to 3.79]
Kinoshita et al 17	DB, PC	4 weeks	483	VON 10 mg, PBO	Proportion of days free of heartburn symptoms	ITT: VON 72.55%, PBO 61.50% (P = .0643) PP: VON 73.60%, PBO 61.40% (P = .0341)
Xiao et al 18	DB, MC	8 weeks (maximum)	468	VON 20 mg, LAN 30 mg	Erosive esophagitis healing rate at 8 weeks	VON 92.4%, LAN 91.3%; DIFF 1.1% [95% CI: −3.822 to 6.087]
Laine et al 19	DB, MC	8 weeks (healing) 24 weeks (maintenance)	1027 878	VON 20 mg, LAN 30 mg VON 20 mg, VON 10 mg, LAN 15 mg	Erosive esophagitis healing rates Erosive esophagitis healing maintenance	VON 92.9%, LAN 84.6%; DIFF 8.3% [95% CI: 4.5 to 12.2; P = .0001] VON 20 mg 80.7%, LAN 72%; DIFF 8.7% [95% CI: 1.8 to 15.2; P = .0001] VON 10 mg 79.2%, LAN 72%; DIFF 7.2% [95% CI: 0.2 to 14.1; P = .0001]
Chey et al 20	MC, OL (DT a ), DB (TT b )	2 weeks	1046	VON 20 mg DT a , VON 20mg TT a , LAN 30 mg TT a	H pylori eradication rates in patients without clarithromycin and amoxicillin-resistant strains	VON TT 84.7%, LAN TT 78.8%; DIFF 5.9% [95% CI: −0.8 to 12.6; P < .001] VON DT 78.5%, LAN TT 78.8%; DIFF −0.3% [95% CI: −7.4 to 6.8; P = .007]
Bunchorntavakul and Buranathawornsom 21	OL	1-2 weeks	122	VON 20 mg twice daily x 7 days OR OMEP 20 mg twice daily x 14 days WITH amoxicillin 1000 mg twice daily AND clarithromycin 500 mg twice daily	H pylori eradication rate	ITT: VON 96.7%, OMEP 88.5% (P = .083) PP: VON 98.3%, OMEP 93.1% (P = .159)
Ang et al 22	OL	1-2 weeks	252	VON 20 mg twice daily × 7 days OR PPI (OMEP 20 mg twice daily OR ESO 20 mg twice daily OR RAB 20 mg twice daily) × 14 days WITH amoxicillin 1000 mg twice daily AND clarithromycin 500 mg twice daily	H pylori eradication rate	ITT: VON 87.4%, PPI 88.0%; DIFF −.64% [95% CI: −8.5 to 7.2] PP: VON 96.3%, PPI 94%; DIFF 2.3% [−1.8 to 8.5]

Abbreviations: DB, double blind; DD, double dummy; DU, duodenal ulcer; ESO, esomeprazole; ITT, intention to treat analysis; LAN, lansoprazole; MC, multicenter; OL, open label; OMEP, omeprazole; PBO, placebo; PC, placebo controlled; PG, parallel group; PP, per protocol analysis; PPI, proton pump inhibitor; RAB, rabeprazole; VON, vonoprazan.

^aVonoprazan 20 mg twice daily plus amoxicillin 1000 mg 3 times daily.

^bVonoprazan 20 mg OR lansoprazole 30 mg twice daily plus amoxicillin 1000 mg twice daily and clarithromycin 500 mg twice daily.

Phase 3 Clinical Trials

A study by Hou and colleagues examined the safety and efficacy of vonoprazan compared to lansoprazole in treating duodenal ulcers. ¹⁶ In this study, 531 Asian patients were randomized to receive vonoprazan 20 mg once daily or lansoprazole 30 mg once daily for 6 weeks. Patients positive for H pylori (approximately 85%) received bismuth-containing quadruple therapy with vonoprazan 20 mg twice daily or lansoprazole 30 mg twice daily for 2 weeks, then vonoprazan or lansoprazole as monotherapy for the remaining 4 weeks. Primary endpoints included duodenal ulcer-healing rates at week 4 and 6; H pylori eradication rates were also evaluated as a secondary endpoint. Duodenal ulcer-healing rates were similar between groups with a difference of 0.4% between groups (95% CI: −3.00, 3.79), indicating noninferiority of vonoprazan. H pylori eradication rates were similar between groups occurring in 91.5% of vonoprazan patients and 86.8% of lansoprazole patients (difference 4.7% [95% CI: −1.28, 10.69]). Tolerability was similar between groups with 74.1% of patients in the vonoprazan group and 64.9% of patients in the lansoprazole group reporting at least one treatment emergent adverse effect. The rate of treatment discontinuation due to adverse effects was 1.5% in the vonoprazan group and 2.2% in the lansoprazole group. Safety was similar between groups with no significant changes in laboratory values, electrocardiograph (ECG), or vital signs.

Kinoshita and colleagues investigated the safety and efficacy of vonoprazan in Japanese patients with nonerosive gastroesophageal reflux disease. ¹⁷ Four hundred eighty-three patients were randomized in a double-blind fashion to receive either vonoprazan 10 mg daily or placebo for 4 weeks. The primary outcome of this study was the proportion of days without heartburn during the treatment phase. Secondary outcomes included cumulative improvement rates of heartburn symptoms and safety. After 4 weeks of treatment, the proportion of heartburn-free days was similar between the vonoprazan and placebo groups. However, cumulative improvement rates of heartburn symptoms were significantly higher in the vonoprazan group when compared to placebo. Adverse effect rates were similar between groups with 23.3% of patients in the placebo group and 23.5% of patients in the vonoprazan group reporting treatment emergent adverse effects. Viral upper respiratory tract infection was the only adverse effect reported in more than 2% of patients. Most adverse effects in either group were mild in nature with only 2 patients in the placebo group and 3 patients in the vonoprazan group withdrawing from the study due to adverse effects.

A clinical trial examining the safety and efficacy of vonoprazan compared to lansoprazole was conducted by Xiao and colleagues in Asian patients with erosive esophagitis. ¹⁸ In this study, 468 patients were randomized to receive vonoprazan 20 mg or lansoprazole 30 mg once daily for up to 8 weeks. The primary outcome measure was erosive esophagitis healing rates. After 8 weeks of treatment, healing rates were 92.4% and 91.3% in the vonoprazan and lansoprazole groups, respectively. The difference between groups was not significant and demonstrated noninferiority of vonoprazan compared to lansoprazole. Adverse effect rates were similar between groups (38.1% in the vonoprazan group and 36.6% in the lansoprazole group) with most patients reporting mild adverse effects. Although serious adverse effects were experienced by 3 patients in each group, these were not found to be attributed to either study medication.

A trial conducted at several sites in the United States examined the efficacy of vonoprazan compared to lansoprazole on healing and maintenance of healing of erosive esophagitis. ¹⁹ In this study, 1027 patients with erosive esophagitis were randomized to receive vonoprazan 20 mg daily or lansoprazole 30 mg daily for up to 8 weeks. Patients who experienced healing (n = 878) were then randomized to receive one of the following regimens: vonoprazan 20 mg daily, vonoprazan 10 mg daily, or lansoprazole 15 mg daily for 24 weeks. Primary endpoints were healing rates by week 8 in the initial cohort of patients and maintenance of healing at week 24 in the patients randomized after the initial phase. Results of the initial 8-week phase showed vonoprazan to be noninferior to lansoprazole in healing rates with 92.9% of patients in the vonoprazan group and 84.6% of patients in the lansoprazole group experiencing healing (difference 8.3% [95% CI 4.5%, 12.2% P = .0001]). Maintenance of healing rates after 24 weeks were 80.7%, 79.2%, 72.0% in the vonoprazan 20 mg, vonoprazan 10 mg, and lansoprazole 15 mg groups, respectively. Both doses of vonoprazan were found to be noninferior to lansoprazole treatment (vonoprazan 20 mg group {difference 8.7% [95% CI 1.8%, 15.5% P = .0001]}, vonoprazan 10 mg group {difference 7.2% [95% CI 0.2%, 14.1% P = .0001]}). Adverse effects were similar between groups with 30.2% of patients treated with vonoprazan and 29.2% of patients treated with lansoprazole reporting adverse effects in the healing phase and 56.4% of patients in the vonoprazan 20 mg group, 54.1% of patients in the vonoprazan 10 mg group, and 50.5% of patients in the lansoprazole group experiencing adverse effects in the maintenance phase. Diarrhea was the most common adverse effect in the healing phase while COVID-19 infection was most common during the maintenance phase. Treatment discontinuation due to adverse effects occurred in 1% of vonoprazan-treated patients and 2.2% of lansoprazole-treated patients in the healing phase and 2.7%, 0.7%, and 0.7% of patients in the vonoprazan 20 mg, vonoprazan 10 mg, and lansoprazole 15 mg groups, respectively.

Chey et al ²⁰ conducted a clinical trial involving American and European patients evaluating the efficacy of 2 vonoprazan-containing H pylori regimens compared to a lansoprazole-containing regimen over a 2-week period. In this trial, 1046 patients were randomized to receive one of the following regimens: open-label dual therapy of 20 mg vonoprazan twice daily with 1000 mg amoxicillin 3 times daily, or double-blind triple therapy of vonoprazan 20 mg twice daily with 1000 mg amoxicillin twice daily and 500 mg clarithromycin twice daily, or double-blind therapy of lansoprazole 30 mg twice daily with 1000 mg amoxicillin twice daily and 500 mg clarithromycin twice daily. The primary outcome was eradication rates in patients without amoxicillin-resistant or clarithromycin-resistant H pylori strains. Secondary outcomes included eradication rates in patients with clarithromycin-resistant H pylori strains and in all patients combined. Both vonoprazan groups exhibited noninferior eradication rates compared to patients taking the lansoprazole-containing triple therapy. When evaluating the secondary outcomes, both vonoprazan-containing regimens were superior to those containing lansoprazole in eradication rates. Rates of adverse effects were similar between groups with 34.1%, 29.9%, and 34.5% of patients reporting treatment-emergent adverse effects in the vonoprazan triple-therapy, vonoprazan dual-therapy, and lansoprazole triple-therapy groups, respectively. The most common adverse effects occurring in ≥5% of patients in any group included diarrhea, nausea, and headache.

Clinical Trials Comparing 7-Day Vonoprazan Regimen to 14-Day PPI Regimen for H pylori Eradication

A study by Bunchorntavakul and colleagues compared the H pylori eradication rates of a 7-day vonoprazan containing regimen with a 14-day PPI-containing regimen in a population of Thai patients. ²¹ Patients were randomized 1:1 to receive one of the following regimens: vonoprazan 20 mg twice daily with amoxicillin 1000 mg twice daily and clarithromycin 500 mg twice daily for 7 days or omeprazole 20 mg twice daily with amoxicillin 1000 mg twice daily and clarithromycin 500 mg twice daily for 14 days. The primary outcome was H pylori eradication rates indicated by urea breath test conducted 4 to 6 weeks after treatment. Of the 122 H pylori-positive treatment-naïve patients randomized, 61 patients received the 7-day treatment and 61 patients received the 14-day treatment. Eradication rates were 96.7% and 88.5% in the 7-day and 14-day treatment regimens, respectively (P = .083). Overall adverse effects reported by ≥5% of patients in any group were bitter taste, nausea, bloating, diarrhea, abdominal pain, and dizziness.

Another trial examining a 7-day vonoprazan-containing regimen to a 14-day PPI-based regimen was conducted by Ang and colleagues. ²² In this trial, 244 Asian patients received either amoxicillin 1000 mg twice daily with clarithromycin 500 mg twice daily and either vonoprazan 20 mg twice daily for 7 days or a PPI for 14 days. Patients randomized to the PPI group were further randomized 1:1:1 to one of the following PPI regimens: omeprazole 20 mg twice daily, esomeprazole 20 mg twice daily, or rabeprazole 20 mg twice daily. The primary outcome was H pylori eradication as demonstrated by urea breath test at least 4 weeks after treatment. H pylori eradication rates were similar between groups in both the intention to treat and per-protocol analysis. Furthermore, the per-protocol analysis showed vonoprazan was noninferior to all 3 of the PPIs used. The most common adverse effects (reported in ≥5% of patients in any group) were loose stools, bloating, constipation, nausea, dyspepsia, and bitter taste. No adverse effects required discontinuation of treatment or hospitalization.

Safety

The most common adverse effects (occurring in ≥2% of patients) associated with vonoprazan dual pak (vonoprazan and amoxicillin) or vonoprazan triple pak (vonoprazan, amoxicillin, and clarithromycin) include nasopharyngitis, diarrhea, constipation, flatulence, dyspepsia, headache, and abdominal pain. More serious adverse effects (occurring in <2% of patients) include, but are not limited to, blood disorders (anemia and neutropenia), bone fractures, infections, and cardiac abnormalities (QT prolongation).^4,23-25 Short-term clinical trials reveal no effect of vonoprazan on liver function. Nonetheless, as previous agents in this class were known to cause hepatotoxicity, liver function should be closely monitored in patients taking vonoprazan. ²⁴ According to the package insert, vonoprazan should be avoided in patients with moderate to severe hepatic impairment as well as those with severe renal impairment. ⁴ Vonoprazan has been shown to increase serum gastrin levels 2 to 3 times more than PPIs. ²⁵ Although the long-term effects of the resulting hypergastrinemia are unknown, caution should be exercised as hypergastrinemia is a known contributor to gastrointestinal malignancies.^5,25 The safety of vonoprazan in pregnancy is unknown; however, animal studies suggest no teratogenic effects of the medication at therapeutic doses. ⁵

In the United States, vonoprazan is only available in combination with other H pylori eradication therapies. Therefore, precautions associated with amoxicillin or clarithromycin are important to consider. Patients who have experienced anaphylaxis or other serious reactions to amoxicillin and/or clarithromycin should avoid this treatment regimen. Other precautions to amoxicillin use include an increased risk of severe cutaneous reactions as well as C. difficile infection. Owing to the clarithromycin component, patients with a history of cholestatic jaundice or hepatic dysfunction should avoid using this treatment regimen. In addition, caution should be exercised in those with a history of QT prolongation or myasthenia gravis and in those who are of child-bearing potential. ⁴

Drug Interactions

As vonoprazan alters the acidity of the stomach, it may attenuate the bioavailability of medications which require an acidic environment and possibly reduce their effectiveness (ex: antiretroviral therapy). Prescribing information of concomitant medications should be reviewed to determine if gastric acidity is required for appropriate drug absorption. Concomitant use of acid-dependent medications should be avoided at this time. ⁴ Vonoprazan is considered a weak inhibitor of CYP2C19 and may either decrease the plasma concentrations of active metabolites of concomitant medications metabolized through CYP2C19 or increased exposure of said medications. However, vonoprazan is not expected to cause relevant CYP2C19-based interactions of clinical relevance. ⁴ Furthermore, there is a lack of evidence to support a clinically significant interaction with clopidogrel, a P2Y12 inhibitor with a noted interaction with other acid-suppressing therapy namely PPIs, as vonoprazan did not display adequate inhibitory effects on the active metabolite of clopidogrel. ²⁶ Therefore, avoidance is not necessary, however, careful monitoring is recommended. CYP3A4 inducers may reduce the effectiveness and drug exposure of vonoprazan and concomitant use of moderate to strong inducers should be avoided. ⁴ As the products approved in the United States additionally contain clarithromycin and amoxicillin, concomitant medications should be screened for potential drug interactions with those agents.

Dosing and Administration

Vonoprazan is packaged in 2 available regimens (Dual Pak and Triple Pak) both of which are indicated for the treatment of H pylori infection in adults. The Dual Pak consists of vonoprazan to be taken at a dose of 20 mg by mouth twice daily along with amoxicillin 1000 mg by mouth 3 times daily for a total of 14 days. The Triple Pak consists of vonoprazan 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg all to be taken by mouth twice daily for a total of 14 days. Dose adjustments are not needed for either renal dysfunction or mild hepatic impairment; however, the use should be avoided with eGFR < 30 mL/min or in moderate to severe hepatic impairment (Child Pugh B or C). ⁴ The Triple-Pak-containing clarithromycin should be avoided if risk factors for macrolide resistance are present such as prior exposure to macrolides, resistance rates above 15%, or eradication rates ≤85%. ³ If a dose is missed, the dose should be taken within 4 hours of the scheduled dose that was missed. If greater than 4 hours since the missed dose, the dose should be skipped and the dosing regimen should be resumed. ⁴ Timing of food consumption is another important consideration with acid-suppressant therapy. However, plasma concentration and drug exposure between both fed and fasting states were similar with vonoprazan administration and therefore can be administered independent of food. ⁸ Vonoprazan is not dose-adjusted based on drug interactions; however, as previously discussed, depending on the medication, the interaction could lead to avoidance of vonoprazan, increased monitoring, or adjustment to the interacting medication.

Place in Therapy

Guidelines for the treatment of H pylori infection published by the American College of Gastroenterology in 2017 list several regimens as first-line therapy all of which contain a PPI as the antisecretory therapy. ³ Successful completion of these regimens, and thus eradication rates, may be limited by adherence (due to the significant pill burden), adverse effects of the individual agents, as well as duration of therapy (10-14 days). The current FDA-approved vonoprazan regimens carry some of these same concerns (especially duration of treatment and pill burden). However, future research investigating the use of 7-day regimens including vonoprazan versus 14-day regimens including PPIs are underway with initial results showing promise.^21,22

Conclusion

Potassium-competitive acid blockers may be safe-and-effective alternative antisecretory agents for H pylori eradication regimens, as well as other gastrointestinal disorders. Vonoprazan is the first P-CAB approved in the United States for the treatment of H pylori infection in adults in combination with amoxicillin (with or without clarithromycin). Phase 3 clinical trials have shown vonoprazan to be as efficacious as the PPIs with a similar adverse effect profile. Initial studies have demonstrated that 7-day vonoprazan-based regimens are noninferior to 14-day PPI-based regimens in eradication rates. Further studies using vonoprazan as the antisecretory agent in H pylori eradication regimens, as well as postmarketing surveillance, will help further elucidate the role of vonoprazan and define long-term risks associated with this agent.