Vonoprazan Fumarate

1 INDICATIONS AND USAGE VOQUEZNA is indicated: for healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults. to maintain healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults. for the relief of heartburn associated with non-erosive gastroesophageal reflux disease in adults. in combination with amoxicillin and clarithromycin for the treatment of Helicobacter pylori ( H. pylori ) infection in adults. in combination with amoxicillin for the treatment of H. pylori infection in adults. VOQUEZNA is a potassium-competitive acid blocker indicated: for healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults. ( 1 ) to maintain healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults. ( 1 ) for the relief of heartburn associated with non-erosive gastroesophageal reflux disease in adults. ( 1 ) in combination with amoxicillin and clarithromycin for the treatment of Helicobacter pylori (H. pylori) infection in adults. ( 1 ) in combination with amoxicillin for the treatment of H. pylori infection in adults. ( 1 )

2 DOSAGE AND ADMINISTRATION Recommended Dosage : Healing of Erosive Esophagitis: 20 mg once daily for 8 weeks. ( 2.1 ) Maintenance of Healed Erosive Esophagitis: 10 mg once daily for up to 6 months. ( 2.1 ) Relief of Heartburn Associated with Non-Erosive Gastroesophageal Reflux Disease: 10 mg once daily for 4 weeks. ( 2.1 ) Treatment of H. pylori Infection: see full prescribing information. ( 2.1 ) See also full prescribing information for the recommended dosage by indication for patients with renal or hepatic impairment. ( 2.2 , 2.3 ) Administration Instructions : Take with or without food. ( 2.4 ) Swallow whole; do not chew or crush. ( 2.4 ) 2.1 Recommended Dosage Healing of Erosive Esophagitis The recommended adult oral dosage is VOQUEZNA 20 mg once daily for 8 weeks for the treatment of healing of erosive esophagitis and relief of associated heartburn. Maintenance of Healed Erosive Esophagitis The recommended adult oral dosage is VOQUEZNA 10 mg once daily for up to 6 months for the maintenance of healed erosive esophagitis and relief of associated heartburn. Relief of Heartburn Associated with Non-Erosive Gastroesophageal Reflux Disease The recommended adult oral dosage is VOQUEZNA 10 mg once daily for 4 weeks. Treatment of H. pylori Infection Triple Therapy: The recommended adult oral dosage is VOQUEZNA 20 mg plus amoxicillin 1,000 mg plus clarithromycin 500 mg, each given twice daily (in the morning and evening, 12 hours apart) for 14 days. Dual Therapy: The recommended adult oral dose is VOQUEZNA 20 mg given twice daily (in the morning and evening) plus amoxicillin 1,000 mg three times daily (in the morning, mid-day, and evening) for 14 days. Also refer to the amoxicillin and clarithromycin full prescribing information. 2.2 Recommended Dosage in Patients with Renal Impairment Healing of Erosive Esophagitis The recommended dosage of VOQUEZNA in adult patients with renal impairment is described in Table 1 below [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . Table 1: Recommended VOQUEZNA Dosage in Patients with Renal Impairment: Healing of Erosive Esophagitis Estimated glomerular filtration rate (GFR) Recommended Dosage 30 mL/minute or greater 20 mg once daily Less than 30 mL/minute 10 mg once daily Maintenance of Healed Erosive Esophagitis or Relief of Heartburn Associated with Non-Erosive Gastroesophageal Reflux Disease The recommended dosage of VOQUEZNA in adult patients with renal impairment is the same as for adult patients with normal renal function [see Dosage and Administration (2.1) ] . Treatment of H. pylori Infection The recommended dosage of VOQUEZNA in adult patients with renal impairment is described in Table 2 below [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ]. Table 2: Recommended VOQUEZNA Dosage in Patients with Renal Impairment: Treatment of H. pylori Infection Also refer to the Dosage and Administration section of the amoxicillin and clarithromycin prescribing information for dosage recommendations in patients with renal impairment. Estimated GFR Recommended Dosage 30 mL/minute or greater 20 mg twice daily Less than 30 mL/minute Use is not recommended 2.3 Recommended Dosage in Patients with Hepatic Impairment Healing of Erosive Esophagitis The recommended dosage of VOQUEZNA in adult patients with hepatic impairment is described in Table 3 below [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ] . Table 3: Recommended VOQUEZNA Dosage in Patients with Hepatic Impairment: Healing of Erosive Esophagitis Classification Recommended Dosage Child-Pugh Class A 20 mg once daily Child-Pugh Class B 10 mg once daily Child-Pugh Class C 10 mg once daily Maintenance of Healed Erosive Esophagitis or Relief of Heartburn Associated with Non-Erosive Gastroesophageal Reflux Disease The recommended dosage of VOQUEZNA in adult patients with hepatic impairment is the same as for patients with normal hepatic function [see Dosage and Administration (2.1) ]. Treatment of H. pylori Infection The recommended dosage of VOQUEZNA in adult patients with hepatic impairment is described in Table 4 below [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ]. Table 4: Recommended VOQUEZNA Dosage in Patients with Hepatic Impairment: Treatment of H. pylori Infection Classification Recommended Dosage Child-Pugh Class A 20 mg twice daily Child-Pugh Class B Use is not recommended Child-Pugh Class C Use is not recommended 2.4 Administration Instructions Take VOQUEZNA with or without food [see Clinical Pharmacology (12.3) ] . Swallow VOQUEZNA tablets whole; do not chew or crush the tablet. Missed doses: For the healing or maintenance of healed erosive esophagitis, or the relief of heartburn associated with non-erosive gastroesophageal reflux disease: If a dose is missed, administer VOQUEZNA as soon as possible within 12 hours after the missed dose. If more than 12 hours have passed, skip the missed dose and administer the next dose at the regularly scheduled time. For the treatment of H. pylori infection: If a dose is missed, administer VOQUEZNA as soon as possible within 4 hours after the missed dose. If more than 4 hours have passed, skip the missed dose and administer the next dose at the regularly scheduled time. Continue the normal dosing schedule until the treatment is completed.

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in labeling: Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.2) ] Clostridioides difficile -Associated Diarrhea [see Warnings and Precautions (5.3) ] Bone Fracture [see Warnings and Precautions (5.4) ] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.5) ] Vitamin B12 (Cobalamin) Deficiency [see Warnings and Precautions (5.6) ] Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions (5.7) ] Fundic Gland Polyps [see Warnings and Precautions (5.9) ] Most common adverse reactions in VOQUEZNA-treated patients are: Healing of Erosive Esophagitis (≥2%): gastritis, diarrhea, abdominal distension, abdominal pain, and nausea. ( 6.1 ) Maintenance of Healed Erosive Esophagitis (≥3%): gastritis, abdominal pain, dyspepsia, hypertension, and urinary tract infection. ( 6.1 ) Relief of Heartburn Associated with Non-Erosive Gastroesophageal Reflux Disease (≥2%): abdominal pain, constipation, diarrhea, nausea, and urinary tract infection. ( 6.1 ) Treatment of H. pylori Infection (≥2%): diarrhea, dysgeusia, vulvovaginal candidiasis, abdominal pain, headache, hypertension, and nasopharyngitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Phathom Pharmaceuticals, Inc. at toll-free phone 1-888-775-7428 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Healing of Erosive Esophagitis and Maintenance of Healed Erosive Esophagitis The safety of VOQUEZNA was evaluated in a randomized, active-controlled, double-blind two phase trial for the healing of erosive esophagitis (2 to 8 weeks) and maintenance of healed erosive esophagitis (through 24 weeks) conducted in the United States and Europe [see Clinical Studies (14.1) , (14.2) ] . Adverse reactions reported in at least 2% of patients in the VOQUEZNA 20 mg once daily arm in the healing phase are presented in Table 5 . Table 5: Adverse Reactions Reported in at least 2% of patients in the VOQUEZNA arm. in a Clinical Trial of Adult Patients with All Grades of Erosive Esophagitis The trial was not designed to support comparative claims for VOQUEZNA for the adverse reactions reported in this table. (2 to 8 Week Healing Phase) Adverse Reactions VOQUEZNA 20 mg Once Daily N=514 % Lansoprazole 30 mg Once Daily N=510 % Gastritis Represents a grouped term and includes related terms. 3 2 Diarrhea 2 3 Abdominal distension 2 1 Abdominal pain 2 1 Nausea 2 1 Adverse reactions reported in at least 3% of patients in the VOQUEZNA 10 mg once daily arm of the maintenance phase are shown in Table 6 . Table 6: Adverse Reactions Reported in at least 3% of patients in the VOQUEZNA arm. in a Clinical Trial of Adult Patients with All Grades of Erosive Esophagitis The trial was not designed to support comparative claims for VOQUEZNA for the adverse reactions reported in this table. (24 Week Maintenance Phase) Adverse Reactions VOQUEZNA 10 mg Once Daily N=296 % Lansoprazole 15 mg Once Daily N=297 % Gastritis Represents a grouped term and includes related terms. 6 3 Abdominal pain 4 2 Dyspepsia 4 3 Hypertension 3 2 Urinary tract infection 3 2 COVID-19 COVID-19 was reported in the healing phase in 11 (2%) VOQUEZNA-treated patients and 9 (2%) lansoprazole-treated patients, and in the maintenance phase in 18 (6%) VOQUEZNA-treated patients and 20 (7%) lansoprazole-treated patients. Other Clinical Trials of Erosive Esophagitis Adverse reactions reported in the United States trial were similar to those reported in 4 additional randomized, active-controlled, double-blind studies of vonoprazan compared to lansoprazole conducted outside of the United States (two 8-week trials of healing of erosive esophagitis and two 24-week maintenance of healed erosive esophagitis trials). Relief of Heartburn Associated with Non-Erosive Gastroesophageal Reflux Disease The safety of VOQUEZNA 10 mg once daily for the relief of heartburn associated with non-erosive gastroesophageal reflux disease was evaluated in a randomized, placebo-controlled, double-blind, four-week trial with a 20-week extension phase conducted in the United States [see Clinical Studies (14.3) ] . Patients initially randomized to placebo in the 4-week placebo-controlled phase were re-randomized to VOQUEZNA 10 mg once daily or a higher dosage of VOQUEZNA for 20 weeks in the extension phase. Adverse reactions reported in at least 2% of patients in the VOQUEZNA 10 mg once daily arm in the 4-week placebo-controlled phase are presented in Table 7 . Table 7: Adverse Reactions Reported in at least 2% of patients in the VOQUEZNA arm. in a Clinical Trial of Adult Patients with Non-Erosive Gastroesophageal Reflux Disease (4-week Placebo-Controlled Phase) Adverse Reactions VOQUEZNA 10 mg Once Daily N=259 % Placebo Once Daily N=256 % Abdominal pain Represents a grouped term and includes related terms. 2 2 Constipation 2 1 Diarrhea 2 1 Nausea 2 <1 Urinary tract infection 2 1 Other adverse reactions: Upper respiratory tract infection (4%) and sinusitis (3%) were reported in patients who received VOQUEZNA 10 mg once daily in the 20-week extension phase. COVID-19 COVID-19 was reported in the 4-week placebo-controlled phase in 3 (1%) patients who received VOQUEZNA 10 mg once daily and 3 (1%) patients who received placebo, and in 24 (7%) patients who received VOQUEZNA 10 mg once daily in the 20-week extension phase. Less Common Adverse Reactions Adverse reactions reported in 1% or less of VOQUEZNA-treated patients for the healing or maintenance of healed erosive esophagitis or for the relief of heartburn associated with non-erosive gastroesophageal reflux disease in the United States trials are: Blood and lymphatic system disorders: anemia, lymphocytosis Cardiac disorders: tachycardia Ear and labyrinth disorders: vertigo Gastrointestinal disorders: duodenal polyp, dry mouth, dysphagia, eructation, flatulence, gastric polyps, vomiting General disorders and administrative site conditions: asthenia, peripheral edema Investigations: increased liver enzymes Metabolism and nutritional disorders: diabetes mellitus Musculoskeletal system: bone fracture Nervous system disorders: dizziness, headache, syncope Psychiatric disorders: depression, insomnia Renal and urinary disorders: tubulointerstitial nephritis Skin and subcutaneous tissue disorders: eczema, rash, urticaria Treatment of H. pylori Infection The safety of VOQUEZNA, amoxicillin and clarithromycin was evaluated in 675 adult patients (aged 20 to 82 years) in clinical trials in the United States, Europe, and Japan, and VOQUEZNA and amoxicillin was evaluated in 348 adult patients (aged 20 to 80 years) in a clinical trial in the United States and Europe. All of the patients were screened and found to be positive for H. pylori infection. The safety of VOQUEZNA, amoxicillin, and clarithromycin (triple therapy) and VOQUEZNA and amoxicillin (dual therapy) was evaluated in a randomized, controlled, double-blind (triple therapy)/open-label (dual therapy) study conducted in the United States and Europe in treatment-naïve H. pylori -positive adult patients [see Clinical Studies (14.4) ] . Adverse Reactions Leading to Discontinuation Treatment discontinuation due to an adverse reaction occurred in 2.3% (8/346) of the patients treated with VOQUEZNA, amoxicillin, and clarithromycin; 0.9% (3/348) of the patients treated with VOQUEZNA and amoxicillin; and 1.2% (4/345) of the patients treated with lansoprazole, amoxicillin, and clarithromycin. The most common adverse reactions leading to discontinuation of VOQUEZNA, amoxicillin, and clarithromycin were diarrhea (0.6%) and hypertension (0.6%), and the most common adverse reaction leading to discontinuation of VOQUEZNA and amoxicillin was rash (0.6%). Most Common Adverse Reactions Adverse reactions reported in at least 2% of patients in any treatment arm are described in Table 8 . Table 8: Adverse Reactions Reported in at least 2% of patients in any treatment arm. in Adult Patients with H. pylori Infection These trials were not designed to support comparative claims for VOQUEZNA-containing treatment arms for the adverse reactions reported in this table. Adverse Reactions VOQUEZNA and Amoxicillin VOQUEZNA, Amoxicillin, and Clarithromycin Lansoprazole, Amoxicillin, and Clarithromycin N=348 % N=346 % N=345 % Diarrhea 5 4 10 Dysgeusia Represents a grouped term and includes related terms. 1 5 6 Vulvovaginal candidiasis 2 3 1 Abdominal pain 3 2 3 Headache 1 3 1 Hypertension 1 2 1 Nasopharyngitis 2 <1 1 Less Common Adverse Reactions Other adverse reactions reported in less than 2% of patients treated with VOQUEZNA, amoxicillin, and clarithromycin or VOQUEZNA and amoxicillin are listed below by body system: Blood and lymphatic system disorders: anemia, leukocytosis, leukopenia, neutropenia Cardiac disorders: QT prolongation, tachycardia Eye disorders: orbital edema Gastrointestinal disorders: abdominal distension, constipation, dry mouth, duodenal polyp, duodenal ulcer, dyspepsia, flatulence, gastric ulcer, gastroesophageal reflux disease, hematochezia, large intestine polyp, rectal polyp, nausea, stomatitis, tongue discomfort, vomiting General disorders and administration site conditions: fatigue, pyrexia Immune system disorders: drug hypersensitivity Infections and infestations: anal fungal infection, gastrointestinal viral infection, oral fungal infection, pneumonia, tongue fungal infection, upper respiratory tract infection, urinary tract infection, viral infection Investigations: increased liver function test Metabolism and nutrition disorders: decreased appetite Musculoskeletal system: bone fracture Nervous system disorders: ageusia, dizziness, tension headache Psychiatric disorders: anxiety, depression, insomnia Renal and urinary disorders: renal hypertrophy, tubulointerstitial nephritis Reproductive system and breast disorders: vaginal discharge Respiratory, thoracic and mediastinal disorders: cough, nasal polyps, oropharyngeal pain Skin and subcutaneous tissue disorders: dermatitis, dry skin, rash For more information on adverse reactions and laboratory changes with amoxicillin or clarithromycin, refer to the Adverse Reactions section of the corresponding prescribing information. 6.2 Postmarketing Experience The following additional adverse reactions have been identified during post-approval use of vonoprazan outside of the United States. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and lymphatic system disorders: thrombocytopenia Immune system disorders: anaphylactic shock [see Contraindications (4) ] Infections and infestations: C. difficile (with concomitant antibacterials) Investigation: hypomagnesemia, hypokalemia, hypocalcemia, vitamin B12 deficiency Hepatobiliary disorders: hepatic injury, hepatic failure, jaundice Skin and subcutaneous tissue disorders: drug eruption, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis

12.3 Pharmacokinetics Steady state pharmacokinetic (PK) parameters for vonoprazan 10 mg or 20 mg following once daily administration and vonoprazan 20 mg following twice daily administration from data collected across multiple studies are summarized in Table 12 . Table 12: Mean (%CV) Steady State Pharmacokinetic Parameters For Vonoprazan Following Once or Twice Daily Dosing PK Parameter Vonoprazan 10 mg Vonoprazan 20 mg Once Daily (N=30) Once Daily (N=68) Twice Daily (N=32) T max (h) median (min, max) 1.5 (0.75, 3.0) 2.0 (0.75, 5.0) 3.0 (1.0-6.0) C max (ng/mL) 11.7 (27.5) 26.1 (35.2) 37.8 (36.1) AUC (hr*ng/mL) 92.9 (33.1) AUC 0-24h 230.9 (41.3) 272.5 (30.5) AUC 0-12h t 1/2z (h) 7.7 (27.1) 7.9 (22.6) 6.8 (22.7) CL/F (L/h) 120.2 (35.2) 100.2 (38.3) 81.3 (35.7) V z /F (L) 1270.7 (26.6) 1114.0 (39.6) 782.7 (34.4) C max = Maximum plasma concentration; AUC 0-24h = Area under the plasma concentration-time curve from time 0 to end of the 24-hour dosing interval; AUC 0-12h = Area under the plasma concentration-time curve from time 0 to the end of the 12-hour dosing interval; T max = Time to reach C max, t 1/2 = Elimination half-life, CL/F = Apparent oral clearance, V z /F = Apparent oral volume of distribution Absorption Vonoprazan exhibits time-independent pharmacokinetics and steady state concentrations are achieved by Day 3 to 4. After multiple doses of vonoprazan ranging from 10 to 40 mg (twice the maximum recommended dose) once daily for 7 days in healthy subjects, C max and area under the plasma concentration-time curve (AUC) values for vonoprazan increased in an approximately dose-proportional manner. There is little accumulation in plasma after once daily multiple doses, with an accumulation index ratio of less than 1.2 based on AUC for doses ranging from 10 to 40 mg (twice the maximum recommended dose). Steady state plasma exposure of vonoprazan following 20 mg twice daily dosing (AUC 0-12h = 273 hr*ng/mL, N=10) was approximately 1.8-fold higher compared to the mean estimate from the same subjects on Day 1 (AUC 0-12h = 155 hr*ng/mL, N=10). Effect of Food In a food effect study in healthy subjects (N=24) who received vonoprazan 20 mg, a high-fat meal resulted in a 5% increase in C max , a 15% increase in AUC, and a delay in median T max of 2 hours. These changes are not considered to be clinically significant [see Dosage and Administration (2.4) ] . Distribution Plasma protein binding of vonoprazan ranged from 85 to 88% in healthy subjects and was independent of concentration from 0.1 to 10 mcg/mL. Elimination Metabolism Vonoprazan is metabolized to inactive metabolites via multiple pathways by a combination of cytochrome P450 (CYP) isoforms (predominantly CYP3A4/5, CYP2C19, CYP2D6, and CYP2B6) along with sulfo- and glucuronosyl-transferases. CYP2C19 and CYP2D6 polymorphisms have been evaluated in clinical studies and there were no clinically meaningful differences in the pharmacokinetics of vonoprazan based on either CYP2C19 or CYP2D6 metabolizer status. Excretion Following oral administration of radiolabeled vonoprazan, approximately 67% of the radiolabeled dose (8% as unchanged vonoprazan) was recovered in urine and 31% (1.4% as unchanged vonoprazan) was recovered in feces. Specific Populations Geriatric Patients No clinically meaningful differences in the pharmacokinetics of vonoprazan are predicted in patients 65 years of age and older compared to younger adult patients. Sex, Race, or Ethnicity There were no clinically significant differences in the pharmacokinetics of vonoprazan based on sex or race/ethnicity. Patients with Renal impairment The pharmacokinetics of vonoprazan administered as a single 20 mg dose in patients with mild [eGFR 60 to <90 mL/min/1.73 m 2 (N=8)], moderate [eGFR 30 to <60 mL/min/1.73 m 2 (N=8)], or severe [eGFR 15 to <30 mL/min/1.73 m 2 (N=8)] renal impairment were compared to those with normal renal function [eGFR ≥90 mL/min/1.73 m 2 (N=13)]. Compared to subjects with normal renal function, systemic exposure (AUC 0-inf ) was 1.7-, 1.3-, and 2.4-times greater in patients with mild, moderate, and severe renal impairment, respectively. In subjects requiring dialysis (N=8), AUC 0-inf estimates were 1.3-fold greater compared to estimates from subjects with normal renal function [see Dosage and Administration (2.2) ] . Protein binding of vonoprazan is not affected by impaired renal function. In patients requiring dialysis, vonoprazan was present in the dialysate and represented 0.94% of the dose administered. Patients with Hepatic Impairment The pharmacokinetics of vonoprazan administered as a single 20 mg dose in patients with mild [Child-Pugh Class A (N=8)], moderate [Child-Pugh Class B (N=8)], or severe [Child-Pugh Class C (N=6)] hepatic impairment were compared to those with normal hepatic function (N=12). Compared to subjects with normal hepatic function, systemic exposure (AUC 0-inf ) of vonoprazan was 1.2-, 2.4-, and 2.6-times greater in patients with mild, moderate, and severe hepatic impairment, respectively [see Dosage and Administration (2.3) ] . Protein binding of vonoprazan is not affected by impaired hepatic function. Drug Interaction Studies In Vitro Studies Cytochrome P450 (CYP450) Enzymes In vitro studies have shown that vonoprazan directly and time-dependently inhibits CYP2B6, CYP2C19, and CYP3A4/5. Transporter Systems Vonoprazan inhibits multidrug and toxin extrusion protein 1 (MATE1) and organic cation transporter 1 (OCT1), but only at concentrations higher than clinically relevant. Clinical Studies 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 (N=11), there was no effect on pharmacokinetics of amoxicillin compared to amoxicillin alone. However, vonoprazan C max and AUC 0-12h increased by 87% and 85%, respectively, and clarithromycin C max and AUC 0-12h increased by 64% and 45%, respectively, compared to administration of each component alone. Effect of Vonoprazan on CYP3A4 Substrates When a single oral dose of midazolam 2 mg was administered following vonoprazan 20 mg twice daily for 7 days (N=20), midazolam AUC 0-inf increased 93% compared to administration of midazolam alone. Effect of CYP3A Inhibitors on Vonoprazan When a single dose of 40 mg vonoprazan (twice the maximum recommended dose) was administered with clarithromycin 500 mg twice daily for 7 days (N=16), vonoprazan AUC 0-inf increased 58% compared to administration of vonoprazan alone. Coadministration of Vonoprazan with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or Low-Dose 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. Model-Informed Approaches Effect of CYP3A Inducers on Vonoprazan Vonoprazan exposures are predicted to be 80% lower when co-administered with a strong CYP3A4 inducer such as rifampicin and 50% lower when co-administered with a moderate CYP3A4 inducer such as efavirenz.