1 INDICATIONS AND USAGE VOQUEZNA TRIPLE PAK, is a co-packaged product containing vonoprazan, a potassium-competitive acid blocker (PCAB), amoxicillin, a penicillin class antibacterial, and clarithromycin, a macrolide antimicrobial, indicated for the treatment of Helicobacter pylori (H.

pylori) infection in adults.

( 1.1 ) VOQUEZNA DUAL PAK, is a co-packaged product containing vonoprazan, a PCAB, and amoxicillin, a penicillin class antibacterial, indicated for the treatment of H.

pylori infection in adults.

( 1.1 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of VOQUEZNA TRIPLE PAK, VOQUEZNA DUAL PAK and other antibacterial drugs, VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

( 1.2 ) 1.1 Helicobacter pylori Infection VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK are indicated for the treatment of Helicobacter pylori ( H.

pylori ) infection in adults [see Clinical Studies (14) ].

1.2 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of VOQUEZNA TRIPLE PAK, VOQUEZNA DUAL PAK and other antibacterial drugs, VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy.

In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Drug-Induced Enterocolitis Syndrome (DIES) [see Warnings and Precautions (5.1) ] Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.1) ] Clostridioides difficile -Associated Diarrhea [see Warnings and Precautions (5.1) ] QT Prolongation [see Warnings and Precautions (5.2) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Serious Adverse Reactions Due to Concomitant Use with Other Drugs [see Warnings and Precautions (5.2) ] Exacerbation of Myasthenia Gravis [see Warnings and Precautions (5.2) ] VOQUEZNA TRIPLE PAK : Most common adverse reactions (≥ 2%) were dysgeusia, diarrhea, vulvovaginal candidiasis, headache, abdominal pain, and hypertension.

( 6.1 ) VOQUEZNA DUAL PAK : Most common adverse reactions (≥ 2%) were diarrhea, abdominal pain, vulvovaginal candidiasis, 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.

Adverse Reactions with VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK The safety of VOQUEZNA TRIPLE PAK was evaluated in 675 adult patients (aged 20 to 82 years) in clinical trials in the United States, Europe and Japan and VOQUEZNA DUAL PAK was evaluated in 348 adult patients (aged 20 to 80 years) in a clinical trial in the United States and Europe.

All the patients were screened and found to be positive for H.

pylori infection.

The safety of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK 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.

Patients were randomized 1:1:1 to vonoprazan 20 mg twice daily plus amoxicillin 1,000 mg twice daily plus clarithromycin 500 mg twice daily (VOQUEZNA TRIPLE PAK) or vonoprazan 20 mg twice daily plus amoxicillin 1,000 mg three times daily (VOQUEZNA DUAL PAK) or lansoprazole 30 mg twice daily plus amoxicillin 1,000 mg twice daily plus clarithromycin 500 mg twice daily (LAC) administered for 14 consecutive days.

A total of 346 patients received VOQUEZNA TRIPLE PAK in the study, 348 received VOQUEZNA DUAL PAK and 345 received LAC.

These patients had a mean age of 51 years (range 20 to 87 years); 62.2% were female, 89.3% were White, 7.4% Black or African American, 1.5% were Asian and 1.8% were others with 72.5% non-Hispanic or Latino.

Adverse Reactions Leading to Discontinuation Treatment discontinuation due to an adverse reaction occurred in 2.3% (8/346) of the VOQUEZNA TRIPLE PAK-treated patients, 0.9% (3/348) of the VOQUEZNA DUAL PAK-treated patients and 1.2% (4/345) of the LAC-treated patients.

The most common adverse reactions leading to discontinuation of VOQUEZNA TRIPLE PAK were diarrhea (0.6%) and hypertension (0.6%) and the most common adverse reaction leading to discontinuation of VOQUEZNA DUAL PAK was rash (0.6%).

Most Common Adverse Reactions The adverse reactions occurring in ≥2% of patients are described in Table 3.

Table 3: Adverse Reactions Occurring in ≥2% of Adult Patients Receiving VOQUEZNA DUAL PAK or VOQUEZNA TRIPLE PAK Adverse Reactions VOQUEZNA DUAL PAK VOQUEZNA TRIPLE PAK LAC (N=348) n (%) (N=346) n (%) (N=345) n (%) Diarrhea 18 (5.2) 14 (4.0) 33 (9.6) Dysgeusia Dysgeusia also includes taste disorder.

2 (0.6) 16 (4.6) 21 (6.1) Vulvovaginal candidiasis Vulvovaginal candidiasis includes: urogenital infection fungal, vulvovaginal candidiasis, vulvovaginal mycotic infection, vulvovaginal pruritus, pruritus genital, genital infection fungal.

7 (2.0) 11 (3.2) 5 (1.4) Abdominal pain Abdominal pain includes: abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper.

9 (2.6) 8 (2.3) 10 (2.9) Headache 5 (1.4) 9 (2.6) 5 (1.4) Hypertension Hypertension also includes blood pressure increased.

4 (1.1) 7 (2.0) 3 (0.9) Nasopharyngitis 7 (2.0) 1 (0.3) 3 (0.9) This study was not designed to evaluate meaningful comparisons of the incidence of adverse reactions in the VOQUEZNA DUAL PAK, VOQUEZNA TRIPLE PAK, and LAC treatment groups.

Other Adverse Reactions Other adverse reactions occurring in <2% of patients with VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK 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, nausea, rectal polyp, 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.

6.2 Postmarketing Experience with Components of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK The following adverse reactions have been identified during post-approval use of vonoprazan (outside of the United States), amoxicillin, or clarithromycin (all used separately).

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.

Vonoprazan Blood and lymphatic system disorders: thrombocytopenia.

Immune system disorders: anaphylactic shock, urticaria [see Contraindications (4.1) ].

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, SJS, TEN.

Amoxicillin Infections and infestations: mucocutaneous candidiasis.

Gastrointestinal: Drug-induced enterocolitis syndrome (DIES), black hairy tongue, and hemorrhagic/pseudomembranous colitis.

Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment .

Hypersensitivity reactions: anaphylaxis [see Contraindications (4.1) ].

Serum sickness–like reactions, erythematous maculopapular rashes, erythema multiforme, exfoliative dermatitis, hypersensitivity vasculitis, and urticaria have been reported.

Renal: crystalluria has been reported [see Overdosage (10) ].

Hemic and lymphatic systems: hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, and agranulocytosis have been reported during therapy with penicillins.

These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.

Central nervous system: reversible hyperactivity, agitation, confusion, convulsions, aseptic meningitis, and behavioral changes have been rarely reported.

Miscellaneous: tooth discoloration (brown, yellow, or gray staining) has been reported.

Most reports occurred in pediatric patients.

Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.

Skin and subcutaneous tissue disorders: TEN, SJS, DRESS, AGEP, and linear IgA bullous dermatosis.

Clarithromycin Blood and lymphatic system: thrombocytopenia, agranulocytosis.

Cardiac: ventricular arrhythmia, torsades de pointes.

Ear and labyrinth: deafness was reported chiefly in elderly women and was usually reversible.

Gastrointestinal: pancreatitis acute, tongue discoloration, tooth discoloration was reported and was usually reversible with professional cleaning upon discontinuation of the drug.

Hepatobiliary: hepatic failure, jaundice hepatocellular.

Adverse reactions related to hepatic dysfunction have been reported with clarithromycin .

Infections and infestations: pseudomembranous colitis .

Immune system: anaphylactic reactions, angioedema.

Investigations: prothrombin time prolonged, white blood cell count decreased, INR increased.

Abnormal urine color has been reported, associated with hepatic failure.

Metabolism and nutrition: hypoglycemia has been reported in patients taking oral hypoglycemic agents or insulin.

Musculoskeletal and connective tissue: myopathy rhabdomyolysis was reported and in some of the reports, clarithromycin was administered concomitantly with statins, fibrates, colchicine or allopurinol [see Contraindications (4.2) ].

Nervous system: parosmia, anosmia, paresthesia and convulsions.

Psychiatric: abnormal behavior, confusional state, depersonalization, disorientation, hallucination, manic behavior, abnormal dream, psychotic disorder.

These disorders usually resolve upon discontinuation of the drug.

Renal and urinary: renal failure.

Skin and subcutaneous tissue disorders: TEN, SJS, DRESS, AGEP, Henoch-Schonlein purpura, acne.

Vascular: hemorrhage.