Vonoprazan (Monograph)

Brand name: Voquezna
Drug class: Potassium-competitive Acid Blockers

Introduction

Potassium-competitive acid blocker.

Uses for Vonoprazan

Erosive Esophagitis and Heartburn

Used for healing and maintenance of healing of erosive esophagitis (all grades) and relief of heartburn associated with erosive esophagitis in adults.

Proton-pump inhibitors (PPIs) are generally recommended as drugs of choice for healing and maintenance of healing of erosive esophagitis. 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 approval of the drug.

Helicobacter pylori Infection

Used in combination with amoxicillin (dual therapy) or in combination with amoxicillin and clarithromycin (triple therapy) for the treatment of Helicobacter pylori (H. pylori) infection in adults.

The American College of Gastroenterology (ACG) has published a guideline on the treatment of H. pylori; however, the role of vonoprazan-containing regimens is not addressed because the guidelines were published prior to approval of the drug.

Vonoprazan Dosage and Administration

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).

• Consider monitoring magnesium and calcium levels prior to initiation of vonoprazan in patients with preexisting risk of hypocalcemia (e.g., hypoparathyroidism). Supplement with magnesium and/or calcium, as necessary.

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).

• Consider monitoring magnesium and calcium levels periodically while on treatment in patients with preexisting risk of hypocalcemia (e.g., hypoparathyroidism). Supplement with magnesium and/or calcium, as necessary.

Administration

Administer orally with or without food.

Vonoprazan is available as a single-entity preparation (Voquezna); the drug is also available in fixed combination with amoxicillin (Voquezna Dual Pak) or clarithromycin and amoxicillin (Voquezna Triple Pak) for use in the treatment of H. pylori infection.

Swallow tablets whole; do not chew or crush.

Dosage

Adults

Erosive Esophagitis and Relief of Heartburn

Oral

Healing of erosive esophagitis and relief of heartburn: 20 mg once daily for 8 weeks.

Maintenance of healed erosive esophagitis and relief of heartburn: 10 mg once daily for up to 6 months.

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

Treatment of H. Pylori Infection

Oral

Dual regimen (vonoprazan and amoxicillin): vonoprazan 20 mg twice daily (morning and evening) plus amoxicillin 1000 mg 3 times daily (morning, mid-day, and evening) for 14 days.

Triple regimen (vonoprazan, amoxicillin, and clarithromycin): vonoprazan 20 mg plus amoxicillin 1000 mg plus clarithromycin 500 mg, each given twice daily (morning and evening, 12 hours apart) for 14 days.

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

Special Populations

Geriatric Patients

No specific dosage recommendations.

Hepatic Impairment

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

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

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

Renal Impairment

Healing of erosive esophagitis: In patients with severe renal impairment (eGFR <30 mL/minute), recommended dosage is 10 mg once daily. No dosage adjustment is necessary in patients with mild to moderate renal impairment (eGFR 30–89 mL/minute).

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

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

Cautions for Vonoprazan

Contraindications

• Known hypersensitivity to vonoprazan or any components of the formulation.

• Concomitant use with rilpivirine-containing products.

Warnings/Precautions

Gastric Malignancy

Symptomatic response to therapy does not preclude the presence of gastric malignancy.

Consider additional follow-up and diagnostic testing in patients who have suboptimal response or early symptomatic relapse after completing treatment with vonoprazan. In older patients, also consider endoscopy.

Acute Tubulointerstitial Nephritis

Acute tubulointerstitial nephritis reported. If suspected, discontinue drug and evaluate patients.

Clostridioides difficile-Associated Diarrhea

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

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

Bone Fracture

PPI therapy may be associated with 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).

Bone fractures, including osteoporosis-related fracture, also reported with vonoprazan.

Use shortest duration of therapy appropriate to the condition being treated.

Patients with increased risk of osteoporosis-related fracture should be managed according to established guidelines.

Severe Cutaneous Reactions

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

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

Vitamin B12 (Cobalamin) Deficiency

Long-term use of acid-suppressing drugs can lead to malabsorption of vitamin B12 caused by hypo- or achlorhydria.

Vitamin B12 deficiency reported during postmarketing experience with vonoprazan.

If clinical symptoms consistent with vitamin B12 deficiency observed, consider further workup.

Hypomagnesemia and Mineral Metabolism

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

Consider monitoring magnesium levels prior to and during therapy 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). Treatment of hypomagnesemia may require magnesium replacement and discontinuation of therapy.

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

Interactions with Diagnostic Investigations for Neuroendocrine Tumors

Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity; may cause false positive results in diagnostic investigations for neuroendocrine tumors.

Temporarily discontinue treatment at least 14 days before assessing CgA levels and consider repeating test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), use the same commercial laboratory for testing.

Fundic Gland Polyps

Fundic gland polyps reported; risk increases with long-term use, especially beyond 1 year. Most patients were asymptomatic and fundic gland polyps were identified incidentally on endoscopy.

Use shortest duration of therapy appropriate to the condition being treated.

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.

Specific Populations

Pregnancy

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

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

Lactation

No data regarding presence of vonoprazan in human milk, effects on the breastfed infant, or effects on milk production. Vonoprazan and its metabolites are present in rat milk.

Potential risk of adverse liver effects shown in animal studies with vonoprazan.

Advise patients not to breastfeed during treatment.

Pediatric Use

Safety and effectiveness in pediatric patients not established.

Geriatric Use

No overall differences in safety or effectiveness observed between geriatric patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Hepatic Impairment

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.

Renal Impairment

Systemic exposure to vonoprazan was 1.7-, 1.3-, and 2.4- times greater in patients with mild, moderate, and severe renal impairment, respectively. In subjects requiring dialysis, AUC estimates were 1.3-fold greater.

Common Adverse Effects

Common adverse reactions (≥2%) with vonoprazan when used for healing of erosive esophagitis: gastritis, diarrhea, abdominal distension, abdominal pain, nausea.

Common adverse reactions (≥3%) with vonoprazan when used for maintenance of healed erosive esophagitis: gastritis, abdominal pain, dyspepsia, hypertension, urinary tract infection.

Common adverse reactions (≥2%) with vonoprazan when used for treatment of H. pylori infection: diarrhea, dysgeusia, vulvovaginal candidiasis, abdominal pain, headache, hypertension, nasopharyngitis.

Drug Interactions

CYP3A4/5, CYP2B6, CYP2C19, CYP2C9, and CYP2D6 substrate; also metabolized by sulfo- and glucoronosyl-transferases. Inhibits CYP2B6, CYP2C19, and CYP3A4/5.

Inhibits multidrug and toxin extrusion protein 1 (MATE1) and organic cation transporter 1 (OCT1) at concentrations higher than clinically relevant.

Drugs Affecting or Affected by Hepatic Microsomal Enzymes

CYP3A inhibitors: potential increased exposure of vonoprazan

CYP3A inducers: potential decreased exposure of vonoprazan (by 80% with a strong inducer or 50% with a moderate inducer). Avoid concomitant use.

CYP3A4 substrates: potential increased concentrations of substrate drug, which may increase risk of adverse effects. Monitor concentrations and for adverse reactions related to the substrate drug; dosage adjustment of the substrate drug may be necessary.

Drugs Dependent on Gastric pH for Absorption

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

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

Combination Therapy with Vonoprazan, Amoxicillin, and Clarithromycin

Co-administration of vonoprazan, amoxicillin, and clarithromycin had no effect on pharmacokinetics of amoxicillin. However, peak plasma concentrations and AUC of vonoprazan and clarithromycin increased.

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

Specific Drugs and Laboratory Interactions

Vonoprazan Pharmacokinetics

Absorption

Bioavailability

Steady state concentrations achieved in 3–4 days.

Distribution

Plasma Protein Binding

85–88% protein-bound.

Elimination

Metabolism

Metabolized to inactive metabolites via CYP3A4/5, CYP2B6, CYP2C19, CYP2C9, and CYP2D6, along with sulfo- and glucoronosyl-transferases.

Elimination Route

Approximately 67% of oral dose recovered in urine (8% unchanged) and 31% in feces (1.4% unchanged).

Half-life

6.8 hours.

Stability

Storage

Oral

Tablets

Store at 20–25°C (excursions permitted between 15–30°C).

Actions and Spectrum

• 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.

• Acid suppression enhances the stability and effectiveness of antimicrobials in the treatment of H. pylori infection.

Advice to Patients

• Advise patients to call their healthcare provider if they experience signs and/or symptoms associated with acute tubulointerstitial nephritis.

• Advise patients to immediately call their healthcare provider if they experience diarrhea that does not improve.

• Advise patients to report any fractures, especially of the hip, wrist, or spine to their healthcare provider.

• Advise patients to discontinue vonoprazan and report to their healthcare provider at first appearance of a severe cutaneous adverse reaction or other sign of hypersensitivity.

• 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.

• Advise patients to report any clinical symptoms that may be associated with hypomagnesemia, hypocalcemia, and/or hypokalemia to their healthcare provider.

• Advise patients to report to their healthcare provider if they start treatment with rilpivirine-containing products.

• Advise patients to contact Phathom Pharmaceuticals if exposed to vonoprazan during pregnancy.

• Advise patients to not breastfeed during treatment with vonoprazan.

• Advise patients of important administration instructions, including how to take the tablets and what to do in the event of missed doses.

• 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.

• Inform patients of other important precautionary information.

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.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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