Vonoprazan Fumarate And Amoxicillin

Q: What should I know before taking Vonoprazan Fumarate And Amoxicillin?

5 WARNINGS AND PRECAUTIONS VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK : Hypersensitivity Reactions : Serious and occasionally fatal reactions (e.g., anaphylaxis) have been reported with components of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK. If hypersensitivity reactions occur, discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK and institute immediate therapy (e.g., anaphylaxis management). ( 5.1 ) Acute Tubulointerstitial Nephritis : Discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK and ev

Q: Is Vonoprazan Fumarate And Amoxicillin available over the counter?

Vonoprazan Fumarate And Amoxicillin is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

Prescription

Brand names: VOQUEZNA DUAL PAK, VOQUEZNA TRIPLE PAK

Dosage Form

Other

Manufacturer

Phathom Pharmaceuticals Inc.

About This Medication

11 DESCRIPTION VOQUEZNA TRIPLE PAK contains vonoprazan tablets, 20 mg, amoxicillin capsules, 500 mg, and clarithromycin tablets, 500 mg for oral administration. VOQUEZNA DUAL PAK contains vonoprazan tablets, 20 mg and amoxicillin capsules, 500 mg for oral administration. Vonoprazan Tablets Vonoprazan (as the fumarate), is a potassium-competitive acid blocker (PCAB). Chemically, it is 1 H -pyrrole-3-methanamine, 5-(2-fluorophenyl)- N -methyl-1-(3-pyridinylsulfonyl)-, (2 E )-2-butenedioate (1:1). Its empirical formula is C 17 H 16 FN 3 O 2 S∙C 4 H 4 O 4 with a molecular weight of 461.5. Vonoprazan has the following structure: Vonoprazan fumarate is white to nearly white crystals or crystalline powder which melts at 194.8°C. Vonoprazan fumarate is soluble in dimethyl sulfoxide; sparingly soluble in N,N –dimethylacetamide, slightly soluble in N,N -dimethylformamide, methanol, and water; very slightly soluble in ethanol (99.5); and practically insoluble in 2-propanol, acetone, 1-octanol, and acetonitrile. Each film-coated tablet contains 20 mg of vonoprazan, present as 26.72 mg of vonoprazan fumarate and the following inactive ingredients: ascorbic acid, croscarmellose sodium, ferric oxide red, fumaric acid, hydroxypropyl cellulose, hypromellose, magnesium stearate, mannitol, microcrystalline cellulose, polyethylene glycol 8000, and titanium dioxide. Chemical structure Amoxicillin Capsules Amoxicillin is a penicillin class antibacterial, with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms. Chemically it is (2 S , 5 R , 6 R )-6-[( R )-(-)-2-amino-2-( p- hydroxyphenyl) acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0] heptane-2-carboxylic acid trihydrate. The molecular formula is C 16 H 19 N 3 O 5 S ∙ 3H 2 O and the molecular weight is 419.45. Amoxicillin has the following structure: Each amoxicillin capsule, with yellow opaque cap and body, contains 500 mg amoxicillin as the trihydrate. Inactive ingredients: Capsule shells – ammonium hydroxide, black ferric oxide, gelatin, potassium hydroxide, propylene glycol, shellac, titanium dioxide, and yellow ferric oxide; Capsule contents – magnesium stearate and microcrystalline cellulose. Meets USP Dissolution Test 2. Chemical structure Clarithromycin Tablets Clarithromycin is a semi-synthetic macrolide antimicrobial for oral use. Chemically, it is 6- O -methylerythromycin. The molecular formula is C 38 H 69 NO 13 , and the molecular weight is 747.96. Clarithromycin has the following structure: Clarithromycin is a white to off-white crystalline powder. It is soluble in acetone, slightly soluble in methanol, ethanol, and acetonitrile, and practically insoluble in water. Each clarithromycin tablet contains 500 mg of clarithromycin and the following inactive ingredients: croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, povidone, talc, and titanium dioxide. Chemical structure

Indications & Usage

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.

How It Works

12.1 Mechanism of Action Vonoprazan 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. 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. Vonoprazan does not require activation by acid. Vonoprazan may selectively concentrate in the parietal cells in both the resting and stimulated states. Vonoprazan binds to the active proton pumps in a noncovalent and reversible manner. Amoxicillin is an antibacterial drug. Clarithromycin is a macrolide antimicrobial drug [see Microbiology (12.4) ]. Acid suppression enhances the replication of H. pylori bacteria and the stability and effectiveness of antimicrobials in the treatment of H. pylori infection.

Dosage & Administration

2 DOSAGE AND ADMINISTRATION VOQUEZNA TRIPLE PAK : The recommended dosage is vonoprazan 20 mg plus amoxicillin 1,000 mg plus clarithromycin 500 mg, each given twice daily (morning and evening, 12 hours apart), with or without food, for 14 days. ( 2.1 ) VOQUEZNA DUAL PAK : The recommended dosage is vonoprazan 20 mg twice daily (morning and evening) plus amoxicillin 1,000 mg, three times a day (morning, mid-day, and evening), with or without food, for 14 days. ( 2.2 ) See full prescribing information for the recommended dosage for patients with renal or hepatic impairment. ( 2.3 , 2.4 ) 2.1 Recommended Dosage for VOQUEZNA TRIPLE PAK VOQUEZNA TRIPLE PAK is a co-packaged product containing vonoprazan tablets, amoxicillin capsules, and clarithromycin tablets each given twice daily (in the morning and evening, 12 hours apart) with or without food, for 14 days [see Clinical Pharmacology (12.3) ] . The recommended adult oral dosage of VOQUEZNA TRIPLE PAK is the following: In the morning, take 20 mg of vonoprazan (one oval pale red tablet), 1,000 mg of amoxicillin (two yellow capsules), and 500 mg of clarithromycin (one oval white tablet) In the evening, take 20 mg of vonoprazan (one oval pale red tablet), and 1,000 mg of amoxicillin (two yellow capsules), and 500 mg of clarithromycin (one oval white tablet) 2.2 Recommended Dosage for VOQUEZNA DUAL PAK VOQUEZNA DUAL PAK is a co-packaged product containing vonoprazan tablets and amoxicillin capsules given with or without food, for 14 days [see Clinical Pharmacology (12.3) ] . The recommended adult oral dosage of VOQUEZNA DUAL PAK is the following: In the morning, take 20 mg of vonoprazan (one oval pale red tablet) and 1,000 mg of amoxicillin (two yellow capsules) Mid-day, take 1,000 mg of amoxicillin (two yellow capsules) In the evening, take 20 mg of vonoprazan (one oval pale red tablet) and 1,000 mg of amoxicillin (two yellow capsules) 2.3 Recommended Dosage in Patients with Renal Impairment The recommended dosage of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK in adult patients with renal impairment is described in Table 1 [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ]. Table 1: Recommended Dosage of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK in Patients with Renal Impairment Estimated GFR Recommended Dosage VOQUEZNA TRIPLE PAK VOQUEZNA DUAL PAK 30 mL/minute or greater 20 mg vonoprazan twice daily 1,000 mg amoxicillin twice daily 500 mg clarithromycin twice daily 20 mg vonoprazan twice daily 1,000 mg amoxicillin three times daily Less than 30 mL/minute Use is not recommended 2.4 Recommended Dosage in Patients with Hepatic Impairment The recommended dosage of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK in adult patients with hepatic impairment is described in Table 2 [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ]. Table 2: Recommended Dosage of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK in Patients with Hepatic Impairment Classification Recommended Dosage VOQUEZNA TRIPLE PAK VOQUEZNA DUAL PAK Child-Pugh Class A 20 mg vonoprazan twice daily 1,000 mg amoxicillin twice daily 500 mg clarithromycin twice daily 20 mg vonoprazan twice daily 1,000 mg amoxicillin three times daily Child-Pugh Class B Use is not recommended Child-Pugh Class C Use is not recommended 2.5 Missed Doses If a dose is missed, administer VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK 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 on the regularly scheduled time. Patients should continue the normal dosing schedule until the medication is completed.

Side Effects Overview

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.

Warnings & Precautions

5 WARNINGS AND PRECAUTIONS VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK : Hypersensitivity Reactions : Serious and occasionally fatal reactions (e.g., anaphylaxis) have been reported with components of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK. If hypersensitivity reactions occur, discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK and institute immediate therapy (e.g., anaphylaxis management). ( 5.1 ) Acute Tubulointerstitial Nephritis : Discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK and evaluate patients. ( 5.1 ) Severe Cutaneous Adverse Reactions (SCAR) : Discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK at the first signs or symptoms of SCAR or other signs of hypersensitivity and consider further evaluation. ( 5.1 ) Drug-induced enterocolitis syndrome (DIES) has been reported with use of amoxicillin, a component of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK. If this occurs, discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK and institute appropriate therapy. ( 5.1 ) Clostridioides difficile -associated diarrhea (CDAD) : Evaluate if diarrhea occurs with VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK. ( 5.1 ) VOQUEZNA TRIPLE PAK Due to the Clarithromycin Component : QT Prolongation : Avoid VOQUEZNA TRIPLE PAK in patients with known QT prolongation or receiving drugs known to prolong the QT interval, ventricular arrhythmia ( torsades de pointes ), hypokalemia/hypomagnesemia, significant bradycardia, or taking Class IA or III antiarrhythmics. ( 5.2 ) Hepatotoxicity : Discontinue if signs and symptoms of hepatitis occur with VOQUEZNA TRIPLE PAK. ( 5.2 ) Serious Adverse Reactions Due to Concomitant Use with Other Drugs : Serious adverse reactions can occur with VOQUEZNA TRIPLE PAK due to drug interactions of clarithromycin with colchicine, some lipid lowering agents, some calcium channel blockers, and other drugs. ( 5.2 ) Embryo-Fetal Toxicity : Based on the findings from animal studies and human observational studies in pregnant women treated with clarithromycin, VOQUEZNA TRIPLE PAK is not recommended for use in pregnant women except in clinical circumstances where no alternative therapy is appropriate. ( 5.2 ) Myasthenia Gravis : Exacerbation of myasthenia gravis can occur with VOQUEZNA TRIPLE PAK since it has been reported in patients receiving clarithromycin tablets. ( 5.2 ) 5.1 Warnings and Precautions for VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK Hypersensitivity Reactions Serious and occasionally fatal hypersensitivity reactions (e.g., anaphylaxis, anaphylactic shock, rash, erythema multiforme, and Henoch-Schonlein purpura) have been reported with components of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK [see Contraindications (4.1) ]. Before initiating therapy with VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, macrolide antibacterial drugs or other allergens. Discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK immediately and institute appropriate treatment if hypersensitivity occurs. Acute Tubulointerstitial Nephritis Acute tubulointerstitial nephritis (TIN) has been reported with vonoprazan, a component of VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK [see Adverse Reactions (6.1) ] . If suspected, discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK and evaluate patients with suspected acute TIN. Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with the components of VOQUEZNA TRIPLE PAK: vonoprazan, amoxicillin, and clarithromycin and VOQUEZNA DUAL PAK: vonoprazan and amoxicillin [see Adverse Reactions (6.2) ] . In addition, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported with amoxicillin and clarithromycin. Discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK at the first signs or symptoms of SCAR or other signs of hypersensitivity and consider further evaluation. Drug-Induced Enterocolitis Syndrome Drug-induced enterocolitis syndrome (DIES) has been reported with use of amoxicillin, a component of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK [see Adverse Reactions (6.2) ] , with most cases occurring in pediatric patients ≤18 years of age. DIES is a non-IgE mediated hypersensitivity reaction characterized by protracted vomiting occurring 1 to 4 hours after drug ingestion in the absence of skin or respiratory symptoms. DIES may be associated with pallor, lethargy, hypotension, shock, diarrhea within 24 hours after ingesting amoxicillin, and leukocytosis with neutrophilia. If DIES occurs, discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK and institute appropriate therapy. Clostridioides difficile -Associated Diarrhea Clostridioides difficile- associated diarrhea (CDAD) has been reported with use of acid suppressing therapies and nearly all antibacterial agents, including amoxicillin (component of VOQUEZNA DUAL PAK and TRIPLE PAK) and clarithromycin (component of VOQUEZNA TRIPLE PAK), and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of Clostridioides difficile (C. difficile) . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is confirmed, VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK should be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated. Rash in Patients with Mononucleosis A high percentage of patients with mononucleosis who receive amoxicillin (a component of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK) develop an erythematous skin rash. Avoid use of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK in patients with mononucleosis. Interactions with Diagnostic Investigations for Neuroendocrine Tumors Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Assess CgA levels at least 4 weeks after VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK treatment and consider repeating the test if initial CgA levels are high [see Drug Interactions (7) and Clinical Pharmacology (12.2) ]. Development of Drug-Resistant Bacteria Prescribing VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK in the absence of a proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to the patient, and increases the risk of the development of drug-resistant bacteria. 5.2 Additional Warnings and Precautions for VOQUEZNA TRIPLE PAK Due to the Clarithromycin Component QT Prolongation Clarithromycin (a component of VOQUEZNA TRIPLE PAK) has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving clarithromycin. Fatalities have been reported. Avoid VOQUEZNA TRIPLE PAK in the following patients: Patients with known prolongation of QT interval, ventricular cardiac arrhythmia, including torsades de pointes. Patients receiving drugs known to prolong the QT interval (e.g., pimozide). Patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia and in patients receiving Class IA (e.g., quinidine, procainamide, disopyramide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval [see Use in Specific Populations (8.5) ]. Hepatotoxicity Hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been reported with clarithromycin (a component of VOQUEZNA TRIPLE PAK). This hepatic dysfunction may be severe and is usually reversible. In some instances, hepatic failure with fatal outcome has been reported and generally has been associated with serious underlying diseases and/or concomitant medications. Symptoms of hepatitis can include anorexia, jaundice, dark urine, pruritus, or tender abdomen. Discontinue VOQUEZNA TRIPLE PAK immediately if signs and symptoms of hepatitis occur. Serious Adverse Reactions Due to Concomitant Use of Clarithromycin with Other Drugs Drugs metabolized by CYP3A4 Serious adverse reactions have been reported in patients taking clarithromycin (a component of VOQUEZNA TRIPLE PAK) concomitantly with CYP3A4 substrates. These include colchicine toxicity with colchicine; markedly increased transaminases with lomitapide; rhabdomyolysis with simvastatin, lovastatin, and atorvastatin; hypoglycemia and cardiac arrhythmias (e.g., torsades de pointes ) with disopyramide; and hypotension and acute kidney injury with calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, amlodipine, diltiazem, nifedipine). Most reports of acute kidney injury with calcium channel blockers metabolized by CYP3A4 involved elderly patients 65 years of age or older [see Contraindications (4.2) and Drug Interactions (7) ]. Colchicine Life-threatening and fatal drug interactions have been reported in patients treated with clarithromycin (a component of VOQUEZNA TRIPLE PAK) and colchicine. If co-administration of VOQUEZNA TRIPLE PAK and colchicine is necessary in patients with normal renal and hepatic function, reduce the dose of colchicine. Monitor patients for clinical symptoms of colchicine toxicity. Concomitant administration of VOQUEZNA TRIPLE PAK and colchicine is contraindicated in patients with renal or hepatic impairment [see Contraindications (4.2) and Drug Interactions (7) ]. Lomitapide Concomitant use of VOQUEZNA TRIPLE PAK with lomitapide may increase the risk of elevation in transaminases due to the clarithromycin component. Concomitant use of VOQUEZNA TRIPLE PAK with lomitapide is contraindicated [see Contraindications (4.2) and Drug Interactions (7) ]. If treatment with VOQUEZNA TRIPLE PAK cannot be avoided, therapy with lomitapide must be suspended during the course of treatment. HMG-CoA Reductase Inhibitors (statins) Concomitant use of VOQUEZNA TRIPLE PAK with lovastatin or simvastatin may increase these drug's plasma concentrations due to the clarithromycin component, which may increase the risk of myopathy, including rhabdomyolysis. Cases of rhabdomyolysis have been reported in patients treated concomitantly with clarithromycin (a component of VOQUEZNA TRIPLE PAK) and lovastatin or simvastatin. Concomitant use of VOQUEZNA TRIPLE PAK with lovastatin or simvastatin is contraindicated [see Contraindications (4.2) ] . If treatment with VOQUEZNA TRIPLE PAK cannot be avoided, therapy with lovastatin or simvastatin must be suspended during the course of treatment. Exercise caution when prescribing VOQUEZNA TRIPLE PAK with atorvastatin or pravastatin [see Drug Interactions (7) ] . Hypoglycemic Agents/Insulin Concomitant use of VOQUEZNA TRIPLE PAK, and hypoglycemic agents (such as nateglinide, pioglitazone, repaglinide, or rosiglitazone) and/or insulin can result in significant hypoglycemia due to the clarithromycin component. Carefully monitor glucose levels when these drugs are used concomitantly with VOQUEZNA TRIPLE PAK [see Drug Interactions (7) ]. Quetiapine Concomitant use of VOQUEZNA TRIPLE PAK with quetiapine could result in somnolence, orthostatic hypotension, altered state of consciousness, neuroleptic malignant syndrome, and QT prolongation due to the clarithromycin component. Refer to quetiapine prescribing information for recommended dosage reduction if co-administered with VOQUEZNA TRIPLE PAK [see Drug Interactions (7) ]. Warfarin There is a risk of serious hemorrhage and significant elevations in the international normalized ratio (INR) and prothrombin time when clarithromycin (a component of VOQUEZNA TRIPLE PAK) is used concomitantly with warfarin. Monitor INR and prothrombin times frequently when warfarin is used concomitantly with VOQUEZNA TRIPLE PAK . Benzodiazepines Increased sedation and prolongation of sedation have been reported with concomitant administration when clarithromycin (a component of VOQUEZNA TRIPLE PAK), and triazolobenzodiazepines, such as triazolam and midazolam. Closely monitor patients for signs or symptoms of increased or prolonged central nervous system effects when benzodiazepines such astriazolam or midazolam are used concomitantly with VOQUEZNA TRIPLE PAK [see Drug Interactions (7) ]. Embryo-Fetal Toxicity with Use of VOQUEZNA TRIPLE PAK Based on findings from animal studies and human observational studies in pregnant women with use of clarithromycin, VOQUEZNA TRIPLE PAK is not recommended for use in pregnant women except in clinical circumstances where no alternative therapy is appropriate. If VOQUEZNA TRIPLE PAK is used during pregnancy, or if pregnancy occurs while the patient is taking this drug, advise the patient of the potential risk to the fetus. Clarithromycin demonstrated adverse effects on pregnancy outcome and/or embryo-fetal development, in pregnant animals administered oral clarithromycin. Observational studies in pregnant women also demonstrated adverse effects on pregnancy outcomes, including an increased risk of miscarriage and in some studies an increased incidence of fetal malformations [see Use in Specific Populations (8.1) ]. Exacerbation of Myasthenia Gravis Exacerbation of symptoms of myasthenia gravis and new onset of symptoms of myasthenic syndrome has been reported in patients receiving clarithromycin therapy (a component of VOQUEZNA TRIPLE PAK). Monitor patients for symptoms.

Contraindications

4 CONTRAINDICATIONS VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK : Known hypersensitivity to vonoprazan, amoxicillin or any other beta-lactams, clarithromycin or any other macrolide antimicrobial or any component of VOQUEZNA TRIPLE PAK. ( 4.1 ) Known hypersensitivity to vonoprazan, amoxicillin or any other beta-lactams or any component of VOQUEZNA DUAL PAK. ( 4.1 ) Rilpivirine-containing products. ( 4.1 ) VOQUEZNA TRIPLE PAK Due to the Clarithromycin Component : Pimozide. ( 4.2 ) Lomitapide, lovastatin, and simvastatin. ( 4.2 ) Ergot alkaloids (ergotamine or dihydroergotamine). ( 4.2 ) Colchicine in renal or hepatic impairment. ( 4.2 ) History of cholestatic jaundice/hepatic dysfunction with use of clarithromycin. ( 4.2 ) Lurasidone. ( 4.2 ) 4.1 Contraindications to VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK Hypersensitivity Reactions VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK are contraindicated in patients with a known hypersensitivity to any component of VOQUEZNA TRIPLE PAK: vonoprazan, amoxicillin (or other β-lactam antibacterials, e.g., penicillins and cephalosporins), or clarithromycin (or other macrolide antibacterial drugs, e.g., erythromycin) or VOQUEZNA DUAL PAK: vonoprazan or amoxicillin (or other β-lactam antibacterials, e.g., penicillins and cephalosporins) [see Warnings and Precautions (5.1) ]. Rilpivirine-containing Products VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK are contraindicated with rilpivirine-containing products [see Drug Interactions (7) ]. 4.2 Additional Contraindications to VOQUEZNA TRIPLE PAK Due to the Clarithromycin Component Serious Adverse Reactions/Risks Due to Drug Interactions Because of the clarithromycin component, VOQUEZNA TRIPLE PAK is contraindicated with concomitant use of: Pimozide: There have been postmarketing reports of drug interactions when clarithromycin is co-administered with pimozide, resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes ) most likely due to inhibition of metabolism of these drugs by clarithromycin. Fatalities have been reported [see Warnings and Precautions (5.2) and Drug Interactions (7) ]. Lipid-lowering Agents: Lomitapide, simvastatin, and lovastatin [see Warnings and Precautions (5.2) and Drug Interactions (7) ] Ergot Alkaloids: Ergotamine or dihydroergotamine [see Drug Interactions (7) ] Colchicine in patients with renal or hepatic impairment [see Warnings and Precautions (5.2) and Drug Interactions (7) ] Lurasidone: Coadministration of clarithromycin and lurasidone may lead to an increase in lurasidone exposure and the potential for serious adverse reactions [see Drug Interactions (7) ] . Cholestatic Jaundice/Hepatic Dysfunction VOQUEZNA TRIPLE PAK is contraindicated in patients with a history of cholestatic jaundice or hepatic dysfunction associated with prior use of clarithromycin.

Pharmacokinetics

12.3 Pharmacokinetics Pharmacokinetic (PK) parameters for vonoprazan 20 mg after a single dose (not an approved recommended dosage) and at steady state following twice daily administration are summarized in Table 8. Table 8: Mean (%CV) Pharmacokinetic Parameters for Vonoprazan Following a Single Dose or at Steady State Following Twice Daily Dosing PK Parameter Single Dose (N=10) Steady State (N=32) C max = Maximum plasma concentration; 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. T max (h), median (range) 2.5 (1.0-4.0) 3.0 (1.0-6.0) C max (ng/mL) 25.2 (39.7) 37.8 (36.1) AUC 0-12h (ng*hr/mL) 154.8 (25.2) 272.5 (30.5) t 1/2 (h) 7.1 (10.1) 6.8 (22.7) CL/F (L/h) 97.3 (36.3) 81.3 (35.7) V z /F (L) 1001 (39.6) 782.7 (34.4) Vonoprazan 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 mg (0.5 times the lowest approved recommended single dosage) to 40 mg (2 times the highest approved recommended single dosage) once daily for 7 days in healthy subjects, C max and AUC values for vonoprazan increased in an approximately dose-proportional manner. Steady state mean 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 Day 1 (AUC 0-12h = 155 hr*ng/mL, N=10). Effect of Food: In a food effect study in healthy subjects (N=24) receiving 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. 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 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 (N=8), moderate (N=8), or severe (N=8) renal impairment were compared to those with normal renal function (N=13). Compared to subjects with normal renal function, systemic exposure (AUC ∞ ) 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 ∞ estimates were 1.3-fold greater compared to estimates from subjects with normal renal function [see Dosage and Administration (2.3) ] . 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 ∞ ) 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 (2.4) ]. 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 administration of 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 ∞ increased 93% compared to administration of midazolam alone. Effect of CYP3A Inhibitors on Vonoprazan : When a single 40 mg (2 times the highest approved recommended single dosage) dose of vonoprazan was administered with clarithromycin 500 mg twice daily for 7 days (N=16), vonoprazan AUC ∞ increased 58% compared to administration of vonoprazan 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. Amoxicillin Absorption Amoxicillin is stable in the presence of gastric acid and is rapidly absorbed after oral administration. Orally administered doses of 500-mg amoxicillin capsules result in average peak blood levels 1 to 2 hours after administration in the range of 5.5 mcg/mL to 7.5 mcg/mL, respectively. Distribution Amoxicillin diffuses readily into most body tissues and fluids, with the exception of brain and spinal fluid, except when meninges are inflamed. In blood serum, amoxicillin is approximately 20% protein-bound. Following a 1-gram dose and utilizing a special skin window technique to determine levels of the antibacterial, it was noted that therapeutic levels were found in the interstitial fluid. Metabolism and Excretion The half-life of amoxicillin is 61.3 minutes. Approximately 60% of an orally administered dose of amoxicillin is excreted in the urine within 6 to 8 hours. Detectable serum levels are observed up to 8 hours after an orally administered dose of amoxicillin. Since most of the amoxicillin is excreted unchanged in the urine, its excretion can be delayed by concurrent administration of probenecid. Clarithromycin Absorption For a single 500 mg dose of clarithromycin, food slightly delays the onset of clarithromycin absorption, increasing the peak time from approximately 2 to 2.5 hours. Food also increases the clarithromycin peak plasma concentration by about 24%, but does not affect the extent of clarithromycin bioavailability. Food does not affect the onset of formation of the active metabolite, 14-OH clarithromycin or its peak plasma concentration but does slightly decrease the extent of metabolite formation, indicated by an 11% decrease in AUC. Therefore, clarithromycin may be given without regard to food. In non-fasting healthy human subjects (males and females), peak plasma concentrations were attained within 2 to 3 hours after oral dosing. Distribution Clarithromycin and the 14-OH clarithromycin metabolite distribute readily into body tissues and fluids. There are no data available on cerebrospinal fluid penetration. Because of high intracellular concentrations, tissue concentrations are higher than serum concentrations. Metabolism and Elimination Steady-state peak plasma clarithromycin concentrations were attained within 3 days and were 3 mcg/mL to 4 mcg/mL with a 500 mg dose administered every 8 hours to 12 hours. The elimination half-life of clarithromycin was 5 hours to 7 hours with 500 mg administered every 8 hours to 12 hours. The nonlinearity of clarithromycin pharmacokinetics is slight at the recommended doses of 500 mg administered every 8 hours to 12 hours. With a 500 mg every 8 hours to 12 hours dosing, the peak steady-state concentration of 14-OH clarithromycin is slightly higher (up to 1 mcg/mL), and its elimination half-life is about 7 hours to 9 hours. With any of these dosing regimens, the steady-state concentration of this metabolite is generally attained within 3 days to 4 days. After a 500 mg tablet every 12 hours, the urinary excretion of clarithromycin is approximately 30%. The renal clearance of clarithromycin is, however, relatively independent of the dose size and approximates the normal glomerular filtration rate. The major metabolite found in urine is 14-OH clarithromycin, which accounts for an additional 10% to 15% of the dose with a 500 mg tablet administered every 12 hours. Patients with Hepatic Impairment The steady-state concentrations of clarithromycin in subjects with impaired hepatic function did not differ from those in normal subjects; however, the 14-OH clarithromycin concentrations were lower in the hepatically impaired subjects. The decreased formation of 14-OH clarithromycin was at least partially offset by an increase in renal clearance of clarithromycin in the subjects with impaired hepatic function when compared to healthy subjects. Patients with Renal Impairment The pharmacokinetics of clarithromycin were also altered in subjects with impaired renal function. Drug Interaction Studies Fluconazole: Following administration of fluconazole 200 mg daily and clarithromycin 500 mg twice daily to 21 healthy volunteers, the steady-state clarithromycin C min and AUC increased 33% and 18%, respectively. Clarithromycin exposures were increased and steady-state concentrations of 14-OH clarithromycin were not significantly affected by concomitant administration of fluconazole. Colchicine: When a single dose of colchicine 0.6 mg was administered with clarithromycin 250 mg twice daily for 7 days, the colchicine C max increased 197% and the AUC 0-∞ increased 239% compared to administration of colchicine alone. Atazanavir: Following administration of clarithromycin (500 mg twice daily) with atazanavir (400 mg once daily), the clarithromycin AUC increased 94%, the 14-OH clarithromycin AUC decreased 70%, and the atazanavir AUC increased 28%. Ritonavir: Concomitant administration of clarithromycin and ritonavir (N=22) resulted in a 77% increase in clarithromycin AUC and a 100% decrease in the AUC of 14-OH clarithromycin. Saquinavir: Following administration of clarithromycin (500 mg twice daily) and saquinavir (soft gelatin capsules, 1200 mg tid) to 12 healthy volunteers, the steady-state saquinavir AUC and C max increased 177% and 187% respectively compared to administration of saquinavir alone. Clarithromycin AUC and C max increased 45% and 39% respectively, whereas the 14-OH clarithromycin AUC and C max decreased 24% and 34% respectively, compared to administration with clarithromycin alone. Didanosine: Simultaneous administration of clarithromycin tablets and didanosine to 12 HIV-infected adult patients resulted in no statistically significant change in didanosine pharmacokinetics. Zidovudine: Following administration of clarithromycin 500 mg tablets twice daily with zidovudine 100 mg every 4 hours, the steady-state zidovudine AUC decreased 12% compared to administration of zidovudine alone (N=4). Individual values ranged from a decrease of 34% to an increase of 14%. When clarithromycin tablets were administered two to four hours prior to zidovudine, the steady-state zidovudine C max increased 100% whereas the AUC was unaffected (N=24). Omeprazole: Clarithromycin 500 mg every 8 hours was given in combination with omeprazole 40 mg daily to healthy adult subjects. The steady-state plasma concentrations of omeprazole were increased (C max , AUC 0-24 , and t ½ increases of 30%, 89%, and 34%, respectively), by the concomitant administration of clarithromycin. The plasma levels of clarithromycin and 14-OH clarithromycin were increased by the concomitant administration of omeprazole. For clarithromycin, the mean C max was 10% greater, the mean C min was 27% greater, and the mean AUC 0-8 was 15% greater when clarithromycin was administered with omeprazole than when clarithromycin was administered alone. Similar results were seen for 14-OH clarithromycin, the mean C max was 45% greater, the mean C min was 57% greater, and the mean AUC 0-8 was 45% greater. Clarithromycin concentrations in the gastric tissue and mucus were also increased by concomitant administration of omeprazole. Table 9: Clarithromycin Tissue Concentrations 2 hours after Dose (mcg/mL)/(mcg/g) Treatment N Antrum Fundus N Mucus Clarithromycin 5 10.48 ± 2.01 20.81 ± 7.64 4 4.15 ± 7.74 Clarithromycin + Omeprazole 5 19.96 ± 4.71 24.25 ± 6.37 4 39.29 ± 32.79 Theophylline: In two studies in which theophylline was administered with clarithromycin (a theophylline sustained-release formulation was dosed at either 6.5 mg/kg or 12 mg/kg together with 250 or 500 mg q12h clarithromycin), the steady-state levels of C max , C min , and the AUC of theophylline increased about 20%. Midazolam: When a single dose of midazolam was co-administered with clarithromycin tablets (500 mg twice daily for 7 days), midazolam AUC increased 174% after intravenous administration of midazolam and 600% after oral administration.

Frequently Asked Questions

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 …

2 DOSAGE AND ADMINISTRATION VOQUEZNA TRIPLE PAK : The recommended dosage is vonoprazan 20 mg plus amoxicillin 1,000 mg plus clarithromycin 500 mg, each given twice daily (morning and evening, 12 hours apart), with or without food, for 14 days. ( 2.1 ) VOQUEZNA DUAL PAK : The recommended dosage is vonoprazan 20 mg twice daily (morning and evening) plus amoxicillin 1,000 mg, three times a day (morning, mid-day, and evening), with or without food, for 14 days. ( 2.2 …

5 WARNINGS AND PRECAUTIONS VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK : Hypersensitivity Reactions : Serious and occasionally fatal reactions (e.g., anaphylaxis) have been reported with components of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK. If hypersensitivity reactions occur, discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK and institute immediate therapy (e.g., anaphylaxis management). ( 5.1 ) Acute Tubulointerstitial Nephritis : Discontinue VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK and evaluate patients. ( 5.1 ) Severe Cutaneous Adverse Reactions (SCAR) …

4 CONTRAINDICATIONS VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK : Known hypersensitivity to vonoprazan, amoxicillin or any other beta-lactams, clarithromycin or any other macrolide antimicrobial or any component of VOQUEZNA TRIPLE PAK. ( 4.1 ) Known hypersensitivity to vonoprazan, amoxicillin or any other beta-lactams or any component of VOQUEZNA DUAL PAK. ( 4.1 ) Rilpivirine-containing products. ( 4.1 ) VOQUEZNA TRIPLE PAK Due to the Clarithromycin Component : Pimozide. ( 4.2 ) Lomitapide, lovastatin, and simvastatin. ( 4.2 ) Ergot …

Vonoprazan Fumarate And Amoxicillin is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

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References & Data Sources

• DailyMed — Vonoprazan Fumarate And Amoxicillin drug label (National Library of Medicine)
• openFDA — Vonoprazan Fumarate And Amoxicillin label data (U.S. Food & Drug Administration)
• RxNorm — RXCUI 197517 (NLM Normalized Drug Names)
• NDC Directory — Vonoprazan Fumarate And Amoxicillin (FDA National Drug Code)

Medical Disclaimer

The information on this page is intended for educational purposes only and should not be used as a substitute for professional medical advice, diagnosis, or treatment.

Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication.

Data sources: DailyMed (NLM), openFDA, MFDS