AHFS Class:

• Potassium-competitive Acid Blockers 56:28.18

Generic Name(s):

• Vonoprazan

Vonoprazan is a potassium-competitive acid blocker.1 4

Erosive Esophagitis

Vonoprazan is used for healing and maintenance of healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults.1,5

Clinical Experience

Efficacy of vonoprazan for this indication is based principally on a randomized, active-controlled, double-blind study in 1024 adults with endoscopically-confirmed erosive esophagitis; 66% had mild disease and 34% had moderate to severe disease.1,5 Patients were randomized to receive vonoprazan 20 mg once daily or lansoprazole 30 mg once daily for 2-8 weeks.1,5 Patients with Helicobacter pylori (H. pylori) infection or Barrett's esophagus were excluded.1,5 Patients with endoscopic healing of erosive esophagitis at week 2 entered the maintenance phase of the study; those who did not reach this endpoint continued to receive randomized treatment until week 8.1,5 Endoscopic healing of erosive esophagitis at week 2 or 8 (the primary efficacy outcome) was achieved in 93% of patients treated with vonoprazan compared with 85% of patients treated with lansoprazole, demonstrating noninferiority of vonoprazan to lansoprazole.1,5 Superiority was demonstrated for the subgroup of patients with moderate to severe disease in complete healing of erosive esophagitis at week 2 (a secondary end point); 70% of vonoprazan-treated patients and 53% of lansoprazole-treated patients achieved this outcome.1,5 Vonoprazan also demonstrated noninferiority to lansoprazole with respect to the percentage of 24-hour heartburn-free days through week 8.1,5

Patients who completed the healing phase of the principal efficacy study and had endoscopically-confirmed healed erosive esophagitis at week 2 or week 8 were re-randomized in the maintenance phase to receive vonoprazan 10 mg, vonoprazan 20 mg, or lansoprazole 15 mg once daily.1,5 At 24 weeks, maintenance of healing was achieved in 79% of patients treated with vonoprazan 10 mg and 72% of patients treated with lansoprazole, demonstrating noninferiority of vonoprazan to lansoprazole.1,5 Superiority was demonstrated for the subgroup of patients with moderate to severe disease for this outcome.1,5 The higher dose of vonoprazan (20 mg) did not demonstrate additional treatment benefit to the approved vonoprazan dose of 10 mg for this indication.1,5 Vonoprazan also demonstrated noninferiority to lansoprazole with respect to the percentage of 24-hour heartburn-free days through week 24.1

Results of additional randomized controlled studies also demonstrated noninferiority of vonoprazan compared with lansoprazole for healing of all grades of erosive esophagitis by week 8 and for maintenance of healed erosive esophagitis through week 52.1,6,7,8

Clinical Perspective

Proton-pump inhibitors (PPIs) are generally recommended as the drugs of choice for healing and maintenance of healing of erosive esophagitis.9 The American College of Gastroenterology (ACG) has published a guideline on the diagnosis and management of gastroesophageal reflux disease, which includes recommendations on the treatment of erosive esophagitis; however, the role of vonoprazan is not addressed because the guideline was published prior to availability of the drug.9

Helicobacter pylori Infection

Vonoprazan is used in combination with amoxicillin (dual therapy) or in combination with amoxillin and clarithromycin (triple therapy) for the treatment of H. pylori infection in adults.1,10

Clinical Experience

Efficacy of vonoprazan for the treatment of H. pylori infection is based principally on the results of a randomized, controlled, phase 3 trial in treatment-naïve, H. pylori -positive adults with at least 1 of the following conditions: dyspepsia lasting ≥2 weeks, functional dyspepsia, recent/new diagnosis of peptic ulcer, peptic ulcer not treated for H. pylori infection, or requirement for long-term non-steroidal anti-inflammatory agent (NSAIA) treatment at a stable dose.1,2 Patients were randomized 1:1:1 to receive vonoprazan triple therapy (vonoprazan 20 mg twice daily plus amoxicillin 1000 mg twice daily plus clarithromycin 500 mg twice daily), vonoprazan dual therapy (vonoprazan 20 mg twice daily plus amoxicillin 1000 mg 3 times daily) or triple therapy with lansoprazole 30 mg twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily; each treatment was administered for 14 consecutive days.1,2 Vonoprazan dual therapy was administered open-label, while the remaining treatments were administered in a double-blind fashion.2 The primary endpoint was the proportion of patients with clarithromycin- and amoxicillin-susceptible strains who achieved successful H. pylori eradication.2 Eradication of H. pylori was confirmed with a negative¹³C urea breath test (UBT) test-of-cure at ≥27 days post-therapy.1

A total of 346 patients received vonoprazan triple therapy, 348 patients received vonoprazan dual therapy, and 345 patients received lansoprazole triple therapy.1 The mean ages of patients in the study were 51.8, 50.6, and 51.8 years in the vonoprazan dual therapy, vonoprazan triple therapy, and lansoprazole triple therapy groups, respectively; the majority of patients enrolled in the trial were white and female.1 Eradication rates among patients with clarithromycin- and amoxicillin-susceptible H. pylori strains were 78.5, 84.7, and 78.8% in the vonoprazan dual therapy, vonoprazan triple therapy, and lansoprazole triple therapy groups, respectively.1,2 Among patients with clarithromycin-resistant H. pylori infections, eradication rates were 69.6, 65.8, and 31.9% with vonoprazan dual therapy, vonoprazan triple therapy, and lansoprazole triple therapy, respectively.1 2 Among all patients, eradication rates were 77.2, 80.8, and 68.5% for vonoprazan dual therapy, vonoprazan triple therapy, and lansoprazole triple therapy, respectively.1 2

Clinical Perspective

The American College of Gastroenterology (ACG) published a guideline on the treatment of H. pylori infection in 2017; however, the role of vonoprazan-containing regimens is not specifically addressed because the guideline was published prior to the availability of the drug.5018 The guideline states that treatment for H. pylori infection should be offered to all adult patients who test positive.5018 Selection of a treatment regimen in adults is typically empiric; although resistance testing can be performed and may be useful to guide treatment selection, such tests may not be readily available.5018 Several different regimens have been recommended or suggested for first-line use; the patient's history of previous antibiotic exposure should be considered when selecting an empiric treatment regiman to assess for the possibility of underlying H. pylori resistance.5018 Clarithromycin triple therapy (consisting of a proton pump inhibitor [PPI], clarithromycin, and amoxicillin or metronidazole administered for 14 days) may be used first line in areas where H. pylori resistance is known to be <15% and if the patient has no previous history of macrolide exposure.5018 ACG recommends the use of either bismuth quadruple therapy (consisting of a PPI, bismuth, tetracycline, and a nitroimidazole [tinidazole or metronidazole] administered for 10-14 days) or concomitant therapy (consisting of a PPI, clarithromycin, amoxicillin, and a nitroimidazole administered for 10-14 days) as first-line treatment for H. pylori .5018 Alternative first-line regimens for empiric treatment of H. pylori are suggested in the treatment guideline from ACG as well.5018 The American Gastroenterological Association (AGA) published a clinical practice update on the treatment of refractory H. pylori infection in 2021; the AGA update does not address regimens using vonoprazan, but recommends avoiding clarithromycin-based regimens in patients with refractory H. pylori who have a history of any treatment with macrolides.5022 Vonoprazan is more potent than PPIs in reducing gastric acid and has a longer half-life, but eradication rates with vonoprazan-containing regimens have been suboptimal in patients with clarithromycin-resistant H. pylori .4

General

Pretreatment Screening

• Consider monitoring magnesium levels prior to initiation of vonoprazan in patients expected to be on prolonged treatment and in patients taking drugs that may have increased toxicity in the presence of hypomagnesemia (e.g., digoxin) or drugs that may cause hypomagnesemia (e.g., diuretics).1
• Consider monitoring magnesium and calcium levels prior to initiation of vonoprazan in patients with preexisting risk of hypocalcemia (e.g., hypoparathyroidism).1 Supplement with magnesium and/or calcium, as necessary.1

Patient Monitoring

• Consider monitoring magnesium levels periodically in patients expected to be on prolonged treatment and in patients taking drugs that may have increased toxicity in the presence of hypomagnesemia (e.g., digoxin) or drugs that may cause hypomagnesemia (e.g., diuretics).1
• Consider monitoring magnesium and calcium levels periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism).1 Supplement with magnesium and/or calcium, as necessary.1

Administration

Vonoprazan is administered orally with or without food.1 Swallow the tablets whole; do not chew or crush the tablets.1

Vonoprazan is also available in fixed combination with amoxicillin (Voquezna^® Dual Pak) or in fixed combination with clarithromycin and amoxicillin (Voquezna^® Triple Pak) for use in the treatment of H. pylori infection.1,10

Store vonoprazan tablets at 20-25°C with excursions to 15-30°C permitted.1

Dosage

Erosive Esophagitis and Relief of Heartburn

The recommended adult dosage of vonoprazan for the healing of erosive esophagitis and relief of heartburn is 20 mg once daily for 8 weeks.1

For maintenance of healed erosive esophagitis and relief of heartburn, the recommended adult dosage of vonoprazan is 10 mg once daily for up to 6 months.1

If a dose is missed, administer the dose as soon as possible within 12 hours after the missed dose.1 If more than 12 hours have passed, skip the missed dose and administer the next dose at the regularly scheduled time.1

Treatment of Helicobacter pylori infection

When vonoprazan is used in a dual regimen with amoxicillin for the treatment of H. pylori infection, the recommended adult dosage is vonoprazan 20 mg twice daily (morning and evening) plus amoxicillin 1000 mg 3 times daily (morning, mid-day, and evening) for 14 days.1

When vonoprazan is used in a triple regimen with amoxicillin and clarithromycin for the treatment of H. pylori , the recommended adult dosage is vonoprazan 20 mg plus amoxicillin 1000 mg plus clarithromycin 500 mg, each given twice daily (morning and evening, 12 hours apart) for 14 days.1

If a dose is missed, take the dose as soon as possible within 4 hours of the missed dose.1 If more than 4 hours has passed, skip the missed dose and resume the regular dosing schedule.1 Continue normal dosing schedule until treatment is completed.1

Special Populations

Hepatic Impairment

Healing of erosive esophagitis:In patients with moderate to severe hepatic impairment (Child-Pugh class B or C), the recomnmended dosage of vonoprazan is 10 mg once daily.1 No dosage adjustment is necessary in patients with mild hepatic impairment (Child-Pugh class A).1

Maintenance of healed erosive esophagitis: No dosage adjustment is necessary in patients with any degree of hepatic impairment.1

Treatment of H. pylori infection:In patients with mild hepatic impairment (Child-Pugh class A), recommended dosage is 20 mg once daily.1 Avoid use in patients with moderate to severe hepatic impairment (Child-Pugh class B or class C).1

Renal Impairment

Healing of erosive esophagitis:In patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/minute), the recommended dosage of vonoprazan is 10 mg once daily.1 No dosage adjustment is needed in patients with mild to moderate renal impairment (eGFR 30-89 mL/minute).1

Maintenance of healed erosive esophagitis: No dosage adjustment is necessary in patients with any degree of renal impairment.1

Treatment of H. pylori infection:In patients with eGFR ≥30 mL/minute, no dosage adjustment is necessary.1 Avoid use in patients with eGFR <30 mL/minute.1

Geriatric Patients

The manufacturer makes no specific dosage recommendations for vonoprazan in geriatric patients.1

Contraindications

• Known hypersensitivity to vonoprazan or any component of the formulation.1
• Concomitant use with rilpivirine-containing products.1

Warnings/Precautions

Gastric Malignancy

In adults, symptomatic response to vonoprazan therapy does not preclude the presence of gastric malignancy.1 Consider additional follow-up and diagnostic testing in patients who have a suboptimal response or an early symptomatic relapse after completing treatment; consider perfoming an endoscopy in older patients.1

Acute Tubulointerstitial Nephritis

Acute tubulointerstitial nephritis has been reported with vonoprazan.1 If suspected, discontinue the drug and evaluate patients.1

Clostridioides difficile-Associated Diarrhea

Clostridioides difficile -associated diarrhea (CDAD) has been reported with use of acid suppressing therapies and nearly all antibacterial agents.1

CDAD must be considered in all patients with diarrhea that does not improve.1 Use the shortest duration of therapy appropriate to the condition being treated.1

Bone Fracture

Proton pump inhibitor (PPI) therapy may be associated with an increased risk of osteoporosis-related fractures of the hip, wrist, or spine; risk is increased in patients who receive high dosages (multiple daily doses or long-term therapy).1 Bone fractures, including osteoporosis-related fracture, also have been reported with vonoprazan.1

Use the shortest duration of therapy appropriate to the condition being treated.1 Patients with increased risk of osteoporosis-related fracture should be managed according to established guidelines.1

Severe Cutaneous Reactions

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported with vonoprazan.1

Discontinue vonoprazan at the first sign or symptom of a severe cutaneous adverse reaction or other sign of hypersensitivity and consider further evaluation.1

Vitamin B12 (Cobalamin) Deficiency

Long-term use of acid-suppressing drugs can lead to malabsorption of vitamin B12 caused by hypo- or achlorhydria.1 Vitamin B12 deficiency has been reported during postmarketing experience with vonoprazan.1 If clinical symptoms consistent with vitamin B12 deficiency are observed in patients receiving the drug, consider further workup.1

Hypomagnesemia and Mineral Metabolism

Hypomagnesemia has been reported during postmarketing experience with vonoprazan.1 Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients.1

Consider monitoring magnesium levels prior to initiation of vonoprazan and periodically in patients expected to be on prolonged treatment, in patients taking drugs that may have increased toxicity in the presence of hypomagnesemia (e.g., digoxin), or drugs that may cause hypomagnesemia (e.g., diuretics).1 Treatment of hypomagnesemia may require magnesium replacement and discontinuation of vonoprazan.1

Consider monitoring magnesium and calcium levels prior to initiation of vonoprazan and periodically while on treatment in patients with preexisting risk of hypocalcemia (e.g., hypoparathyroidism).1 Supplement with magnesium and/or calcium, as necessary.1 If hypocalcemia is refractory to treatment, consider discontinuing vonoprazan.1

Interactions with Diagnostic Investigations for Neuroendocrine Tumors

Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity.1 The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors.1 Temporarily discontinue vonoprazan treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high.1 If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary.1

Funic Gland Polyps

Vonoprazan is associated with a risk of fundic gland polyps; the risk increases with long-term use, especially beyond 1 year.1 Fundic gland polyps have been reported with vonoprazan in clinical trials and during postmarketing experience with PPIs.1 Most patients who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy.1 Use the shortest duration of therapy appropriate to the condition being treated.1

Use of Fixed Combinations

When vonoprazan is used in fixed combination with amoxicillin and clarithromycin, consider the cautions, precautions, and contraindications of amoxicillin and clarithromycin.1,10

Specific Populations

Pregnancy

There are no adequate and well-controlled studies of vonoprazan in pregnant women to evaluate for drug-associated risks of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.1

Report pregnancies to the Phathom Pharmaceuticals Adverse Event reporting line at 1-888-775-PHAT (7428).1

Lactation

There are no data regarding the presence of vonoprazan in human milk, the effects on the breastfed infant, or the effects on milk production.1 Vonoprazan and its metabolites are present in rat milk.1 Liver injury occurred in the offspring of pregnant and lactating rats administered oral vonoprazan at exposures approximately equal to and greater than the maximum recommended human dose.1 When a drug is present in animal milk, it is likely that the drug will be present in human milk.1 Because of the potential risk of adverse liver effects shown in animal studies with vonoprazan, advise patients not to breastfeed during treatment with the drug.1

Pediatric Use

Safety and effectiveness of vonoprazan in pediatric patients have not been established.1

Geriatric Use

There were 200 patients 65 years of age and older in the clinical trial of vonoprazan for erosive esophagitis and relief of heartburn; among patients who received vonoprazan, 18% were 65 years of age or older and 2% were 75 years of age or older.1

There were 218 patients 65 years of age and older in the clinical trial for the treatment of H. pylori infection; among patients who received vonoprazan, 22% were 65 years of age or older and 3% were 75 years of age or older.1 No overall differences in safety or effectiveness were observed between these patients and younger adult patients, and other reported clinical experience has not identified differences in responses between geriatric and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out.1

No clinically meaningful differences in the pharmacokinetics of vonoprazan are expected in patients 65 years of age and older compared to younger adult patients.1

Renal Impairment

Compared to subjects with normal renal function, systemic exposure to vonoprazan was 1.7-, 1.3-, and 2.4- times greater in patients with mild, moderate, and severe renal impairment, respectively.1 In patients requiring dialysis, AUC estimates were 1.3-fold greater compared to estimates from subjects with normal renal function.1

Hepatic Impairment

Compared to subjects with normal hepatic function, systemic exposure to vonoprazan was 1.2-, 2.4-, and 2.6-times greater in patients with mild (Child-Pugh class A), moderate (Child-Pugh class B), and severe (Child-Pugh class C) hepatic impairment, respectively.1

Common Adverse Effects

The most common adverse reactions (≥2%) associated with vonoprazan when used for healing of erosive esophagitis include gastritis, diarrhea, abdominal distension, abdominal pain, and nausea.1

The most common adverse reactions (≥3%) associated with vonoprazan when used for maintenance of healed erosive esophagitis include gastritis, abdominal pain, dyspepsia, hypertension, and urinary tract infection.1

The most common adverse reactions (≥2%) associated with vonoprazan when used for the treatment of H. pylori infection include diarrhea, dysgeusia, vulvovaginal candidiasis, abdominal pain, headache, hypertension, and nasopharyngitis.1

Vonoprazan is a substrate of multiple cytochrome P-450 (CYP) isoforms including CYP3A4/5, CYP2B6, CYP2C19, CYP2C9, and CYP2D6; the drug is also metabolized by sulfo- and glucoronosyl-transferases.1

In vitro studies indicate that vonoprazan inhibits CYP2B6, CYP2C19, and CYP3A4/5.1 At concentrations higher than clinically relevant, vonoprazan is a multidrug and toxin extrusion protein 1 (MATE1) and organic cation transporter 1 (OCT1) inhibitor.1

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A

Concomitant use of vonoprazan with CYP3A inhibitors increases the exposure of vonoprazan.1 A single 40-mg dose of vonoprazan administered with clarithromycin 500 mg twice daily for 7 days increased the AUC by 58% compared to administration of vonoprazan alone.1

Inducers of CYP3A

Concomitant use of vonoprazan with CYP3A inducers is predicted to decrease the exposure of vonoprazan.1 Vonoprazan exposures are predicted to be 80% lower when co-administered with a strong CYP3A4 inducer such as rifampicin and 50% when coadministered with a moderate CYP3A4 inducer such as efavirenz.1

Avoid concomitant use of strong or moderate CYP3A inducers with vonoprazan.1

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP3A4

Vonoprazan is a weak CYP3A inhibitor; concomitant use with CYP3A4 substrates can increase systemic exposure and risk of adverse effects associated with the substrate drug.1

Concomitant use of vonoprazan (20 mg twice daily for 7 days) and midazolam (single 2-mg dose) increased midazolam AUC by 93% compared to administration of midazolam alone.1

Monitor concentrations and for adverse reactions related to the substrate drug when used concomitantly with vonoprazan; dosage adjustment of the substrate drug may be necessary.1

Substrates of CYP2C19

Concomitant use of vonoprazan, a CYP2C19 inhibitor, and clopidogrel, citalopram, or cilostazol, may impact plasma concentrations of these agents.1 Plasma concentrations of the active metabolite of clopidogrel may be reduced resulting in a reduction of platelet inhibition.1 Exposure to citalopram and cilostazol may be increased with concomitant use of vonoprazan.1

Carefully monitor the efficacy of clopidogrel and consider alternative antiplatelet therapy.1 Dosage adjustment of citalopram and cilostazol may be required; see the respective prescribing information for dosage adjustment guidelines.1 Carefully monitor for adverse reactions of citalopram and cilostazol.1

Drugs Dependent on Gastric pH for Absorption

Vonoprazan reduces intragastric acidity, which may alter absorption of several drugs dependent on gastric pH for absorption including antiretroviral drugs, iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole, and itraconazole.1

Concomitant use of vonoprazan and rilpivirine-containing products is contraindicated.1 Avoid concomitant use of vonoprazan with atazanavir or nelfinavir.1 Refer to prescribing information of other drugs dependent on gastric pH for absorption prior to use of vonoprazan.1

NSAIAs and Aspirin

When a single dose of 40 mg vonoprazan (twice the maximum recommended dose) was co-administered with diclofenac 25 mg, meloxicam 10 mg, or aspirin 100 mg, there were no clinically meaningful changes in exposure of vonoprazan, diclofenac, meloxicam, or aspirin compared to administration of each drug alone.1

Chromgranin A (CgA) Test for Neuroendocrine Tumors

Vonoprazan reduces intragastric acidity, which increases CgA level and may cause false positive results in diagnostic investigations for neuroendocrine tumors.1

Assess CgA levels at least 14 days after vonoprazan treatment and repeat if initial CgA levels are high.1 If serial tests are performed, use the same commercial laboratory for testing.1

Combination Therapy with Vonoprazan, Amoxicillin, and Clarithromycin

When vonoprazan 20 mg, amoxicillin 750 mg, and clarithromycin 400 mg were co-administered twice daily for 7 days, there was no effect on the pharmacokinetics of amoxicillin compared to amoxicillin alone.1 However, peak plasma concentration and AUC of vonoprazan increased by 87% and 85%, respectively, and peak plasma concentration and AUC of clarithromycin increased by 64% and 45% respectively, compared to administration of each component alone.1

Concomitant administration of clarithromycin and other drugs can cause serious adverse reactions, including potentially fatal arrhythmias, and are contraindicated.1 Amoxicillin also has drug interations.1 See the respective prescribing information for additional information.1

Secretin Stimulation Test

Vonoprazan may interact with the secretin stimulation test.1 Hyper-response in gastrin secretion in response to the secretin stimulation test may falsely suggest gastrinoma.1 Temporarily stop vonoprazan at least 14 days before assessing to allow gastrin levels to return to baseline.1

Description

Vonoprazan is a potassium-competitive acid blocker that suppresses basal and stimulated gastric acid secretion at the secretory surface of the gastric parietal cell through inhibition of the H+, K+-ATPase enzyme system in a potassium competitive manner.1,2 Because this enzyme is regarded as the acid (proton) pump within the parietal cell, vonoprazan has been characterized as a type of gastric proton-pump inhibitor, in that it blocks the final step of acid production.1,2 Vonoprazan does not require activation by acid.1 Vonoprazan may selectively concentrate in the parietal cells in both the resting and stimulated states.1 Vonoprazan binds to the active proton pumps in a noncovalent and reversible manner.1 Acid suppression enhances the stability and effectiveness of antimicrobials in the treatment of H. pylori infection.10

Decreased gastric acidity due to any means, increases gastric counts of bacteria normally present in the GI tract.1 Vonoprazan decreases gastric acidity.1 Vonoprazan/amoxicillin may lead to a slightly increased risk of GI infections due to pathogens such as Salmonella and Campylobacter and, in hospitalized patients, possibly also due to C. difficile .1

Steady-state concentrations of vonoprazan are achieved within 3-4 days.1 Vonoprazan is 85-88% protein bound.1 Vonoprazan is metabolized to inactive metabolites via multiple cytochrome P-450 (CYP) isoforms including CYP3A4/5, CYP2B6, CYP2C19, CYP2C9, and CYP2D6 along with sulfo- and glucuronosyl-transferases.1 Approximately 67% of an oral dose of vonoprazan was recovered in urine (8% as unchanged) and 31% in feces (1.4% as unchanged).1 The half-life of the drug at steady-state is approximately 6.8 hours.1

Advice to Patients

• Advise patients to call their healthcare provider if they experience signs and/or symptoms associated with acute tubulointerstitial nephritis.1
• Advise patients to immediately call their healthcare provider if they experience diarrhea that does not improve.1
• Advise patients to report any fractures, especially of the hip, wrist, or spine to their healthcare provider.1
• Advise patients to discontinue vonoprazan and report to their healthcare provider a first appearance of a severe cutaneous adverse reaction or other sign of hypersensitivity.1
• Advise patients to report any clinical symptoms that may be associated with vitamin B12 deficiency to their healthcare provider, if they have been receiving vonoprazan long-term.1
• Advise patients to report any clinical symptoms that may be associated with hypomagnesemia, hypocalcemia, and/or hypokalemia to their healthcare provider.1
• Advise patients to report to their healthcare provider if they start treatment with rilpivirine-containing products.1
• Advise patients to contact Phathom Pharmaceuticals if exposed to vonoprazan during pregnancy.1
• Advise patients to not breastfeed during treatment with vonoprazan.1
• Advise patients of important administration instructions, including how to take the tablets and what to do in the event of missed doses.1
• Advise patients to inform clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1
• Inform patients of other important precautionary information.1

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Only references cited for selected revisions after 1984 are available electronically.

1. Phathom Pharmaceuticals. VOQUEZNA (vonoprazan) prescribing information. 2023 Nov.

2. Chey WD, Mégraud F, Laine L, López LJ, Hunt BJ, Howden CW. Vonoprazan Triple and DualTherapy for Helicobacter pylori Infection in the United States and Europe: Randomized Clinical Trial. Gastroenterology. 2022;163(3):608-619. doi:10.1053/j.gastro.2022.05.055

3. Echizen H. The first-in-class potassium-competitive acid blocker, vonoprazan fumarate: pharmacokinetic and pharmacodynamic considerations. Clin Pharmacokinet. 2016;55(4):409-18. [Web]

4. Two vonoprazan combinations (Voquezna) for H. pylori. Med Lett Drugs Ther. 2022 Oct 31;64(1662):169-172. PMID: 36383768.

5. Laine L, DeVault K, Katz P et al. Vonoprazan Versus Lansoprazole for Healing and Maintenance of Healing of Erosive Esophagitis: A Randomized Trial. Gastroenterology. 2023 Jan;164(1):61-71. doi: 10.1053/j.gastro.2022.09.041. Epub 2022 Oct 10. PMID: 36228734.

6. Xiao Y, Zhang S, Dai N et al. Phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of vonoprazan compared with lansoprazole in Asian patients with erosive oesophagitis. Gut. 2020 Feb;69(2):224-230. doi: 10.1136/gutjnl-2019-318365. Epub 2019 Aug 13. PMID: 31409606; PMCID: PMC6984055.

7. Ashida K, Iwakiri K, Hiramatsu N et al. Maintenance for healed erosive esophagitis: Phase III comparison of vonoprazan with lansoprazole. World J Gastroenterol. 2018 Apr 14;24(14):1550-1561. doi: 10.3748/wjg.v24.i14.1550. PMID: 29662293; PMCID: PMC5897859.

8. Ashida K, Sakurai Y, Hori T et al. Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis. Aliment Pharmacol Ther. 2016 Jan;43(2):240-51. doi: 10.1111/apt.13461. Epub 2015 Nov 11. PMID: 26559637; PMCID: PMC4738414.

9. Katz PO, Dunbar KB, Schnoll-Sussman FH et al. ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol. 2022 Jan 1;117(1):27-56. doi: 10.14309/ajg.0000000000001538. PMID: 34807007; PMCID: PMC8754510.

10. Phathom Pharmaceuticals. VOQUEZNA DUAL PAK (vonoprazan fumarate and amoxicillin) and VOQUEZNA TRIPLE PAK (vonoprazan fumarate, amoxicillin, and clarithromycin) prescribing information. 2022 May.

5018. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017;112(2):212-239. [Web]

5020. Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in world health organization regions. Gastroenterology. 2018;155(5):1372-1382. [Web]

5021. Hulten KG, Lamberth LB, Kalfus IN, Graham DY. National and regional US antibiotic resistance to Helicobacter pylori: lessons from a clinical trial. Gastroenterology. 2021;161(1): 342-344. [Web]

5022. Shah SC, Iyer PG, Moss SF. AGA Clinical practice update on the management of refractory Helicobacter pylori infection: expert review. Gastroenterology. 2021;160(5): 1831-1841. [Web]