VOQUEZNA

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 )

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