Vonoprazan Fumarate And Amoxicillin

FDA Drug Information • Also known as: Voquezna Dual Pak

Brand Names: Voquezna Dual Pak
Dosage Form: KIT
Product Type: HUMAN PRESCRIPTION DRUG

Description

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:...

What Is Vonoprazan Fumarate And Amoxicillin Used For?

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.

Dosage and 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...

Side Effects (Adverse Reactions)

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...

Drug Interactions

7 DRUG INTERACTIONS Collated drug interaction information for the individual components in VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK is summarized below. Drug interaction studies with VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK have not been conducted. These recommendations are based on either drug interaction trials or predicted interactions due to the expected magnitude of interaction and potential for serious adverse reactions or loss of efficacy [see Clinical Pharmacology (12.3) ] . Clarithromycin (a component of VOQUEZNA TRIPLE PAK) is a strong CYP3A inhibitor. Concomitant use of VOQUEZNA TRIPLE PAK with a drug(s) primarily metabolized by CYP3A may cause elevations in CYP3A substrate drug's concentrations that could increase or prolong both therapeutic and adverse effects of the concomitant drug. Table 4: Effects of Other Drugs on VOQUEZNA TRIPLE PAK Strong or Moderate CYP3A Inducers Clinical Effect Vonoprazan and clarithromycin are CYP3A substrates. Strong or moderate CYP3A inducers may decrease exposure of vonoprazan and clarithromycin [see Clinical Pharmacology (12.3) ] , which may reduce the effectiveness of VOQUEZNA TRIPLE PAK. Prevention or Management Avoid concomitant use with VOQUEZNA TRIPLE PAK. Probenecid Clinical Effect Amoxicillin undergoes tubular secretion. Probenecid may increase amoxicillin exposure by blocking its renal tubular secretion, which may increase the risk of VOQUEZNA TRIPLE PAK adverse reactions. Prevention or Management Closely monitor for signs or symptoms of increased or prolonged adverse reactions associated with amoxicillin when used with VOQUEZNA TRIPLE PAK. Allopurinol Clinical Effect Increase in the incidence of rashes is reported in patients receiving both allopurinol and amoxicillin together compared to patients receiving amoxicillin alone. It is not known whether this potentiation of amoxicillin rashes is due to allopurinol or the hyperuricemia present in these patients. Prevention or Management Discontinue allopurinol at the first appearance of skin rash when used concomitantly with VOQUEZNA TRIPLE PAK. Omeprazole Clinical Effect Clarithromycin concentrations in the gastric tissue and mucus were increased by concomitant administration of omeprazole [see Clinical Pharmacology (12.3) ] . Prevention or Management Avoid concomitant use of VOQUEZNA TRIPLE PAK with omeprazole. Itraconazole Clinical Effect Both clarithromycin and itraconazole are substrates and inhibitors of CYP3A, potentially leading to a bi-directional drug interaction when administered concomitantly. VOQUEZNA TRIPLE PAK's use with strong CYP3A4 inhibitors may lead to increases in clarithromycin exposure, which may increase the risk of VOQUEZNA TRIPLE PAK adverse reactions. Prevention or Management Patients taking itraconazole with VOQUEZNA TRIPLE PAK should be monitored closely for signs or symptoms of increased or prolonged adverse reactions associated with itraconazole and clarithromycin. Antivirals Clinical Effect Clarithromycin is a...

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...

Pregnancy and Breastfeeding

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK during pregnancy. Healthcare providers are encouraged to register patients by calling 1-866-609-1612 or visiting https://voqueznapregnancyregistry.com/ . Risk Summary VOQUEZNA TRIPLE PAK Based on findings from animal studies and observational studies in pregnant women with use of clarithromycin, use of VOQUEZNA TRIPLE PAK is not recommended in pregnant women except in clinical circumstances where no alternative therapy is appropriate. There are no adequate and well-controlled studies of VOQUEZNA TRIPLE PAK in pregnant women to evaluate for drug-associated risks of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. If VOQUEZNA TRIPLE PAK is used during pregnancy, advise pregnant women of the potential risk to a fetus. No reproductive and developmental toxicity studies with the combination of vonoprazan, amoxicillin, and/or clarithromycin were conducted. VOQUEZNA DUAL PAK There are no adequate and well-controlled studies of VOQUEZNA DUAL PAK in pregnant women to evaluate for drug-associated risks of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Individual Components of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK Clarithromycin: Published observational studies in pregnant women have demonstrated adverse effects on pregnancy outcomes, including an increased risk of miscarriage and in some studies an increased incidence of fetal malformations (see Data ) . In animal reproduction studies, administration of oral clarithromycin to pregnant mice, rats, rabbits, and monkeys during the period of organogenesis produced malformations in rats (cardiovascular anomalies) and mice (cleft palate) at clinically relevant doses. Fetal effects in mice, rats, and monkeys (e.g., reduced fetal survival, body weight, body weight gain) and implantation losses in...

Overdosage

10 OVERDOSAGE No information is available on accidental overdosage of VOQUEZNA TRIPLE PAK or VOQUEZNA DUAL PAK in humans. In case of an overdose, patients should contact a physician, poison control center, or emergency room. The available overdosage information for each of the individual components in VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK are summarized below: Vonoprazan There have been no reports of overdose with vonoprazan. In clinical studies, a single dose of 120 mg resulted in no serious adverse reactions. Vonoprazan is not removed from the circulation by hemodialysis. If overdose occurs, treatment should be symptomatic and supportive. Amoxicillin In case of amoxicillin overdosage, discontinue medication, treat symptomatically and institute supportive measures as needed. A prospective study of 51 pediatric patients at a poison-control center suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms. Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage with amoxicillin. Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin crystalluria. Renal impairment appears to be reversible with cessation of drug administration. High blood levels may occur more readily in patients with impaired renal function because of decreased renal clearance of amoxicillin. Amoxicillin can be removed from circulation by hemodialysis. Clarithromycin Overdosage of clarithromycin can cause gastrointestinal symptoms such as abdominal pain, vomiting, nausea, and diarrhea. Treat adverse reactions accompanying overdosage by the prompt elimination of unabsorbed drug and supportive measures. As with other macrolides, clarithromycin serum concentrations are not...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING VOQUEZNA TRIPLE PAK is a co-package containing: Vonoprazan Tablets, 20 mg: pale red, oval, film-coated tablets debossed V20 on one side and plain on the other side. Amoxicillin Capsules, 500 mg: yellow, opaque, hard gelatin capsules imprinted with AMOX 500 on one side and GG 849 on the other side. Clarithromycin Tablets, 500 mg: white, oval, film-coated tablets debossed GG C9 on one side and plain on the other side. Vonoprazan tablets, amoxicillin capsules, and clarithromycin tablets are supplied in separate blister cavities within the same blister card. Each unit of use carton (NDC 81520-255-14) contains 56 tablets and 56 capsules divided into 14 daily dose blister cards. Each daily blister card contains two vonoprazan tablets (20 mg each), four amoxicillin capsules (500 mg each), and two clarithromycin tablets (500 mg each), and indicates which tablets and capsules need to be taken in the morning and evening. Store between 20°C and 25°C (68°F and 77°F). Brief exposure to 15°C to 30°C (59°F to 86°F) permitted (see USP Controlled Room Temperature). Protect from light. VOQUEZNA DUAL PAK is a co-package containing: Vonoprazan Tablets, 20 mg: pale red, oval, film-coated tablets debossed V20 on one side and plain on the reverse side. Amoxicillin Capsules, 500 mg: yellow, opaque, hard gelatin capsules imprinted with AMOX 500 on one side and GG 849 on the other side. Vonoprazan tablets and amoxicillin capsules are supplied in separate blister cavities within the same blister card. Each unit of use carton (NDC 81520-250-14) contains 28 tablets and 84 capsules divided into 14 daily dose blister cards. Each daily blister card contains two vonoprazan tablets (20 mg each) and six amoxicillin capsules (500 mg each) and indicates which tablets and capsules need to be taken in the morning, mid-day, and evening. Store between 20°C and 25°C (68°F and 77°F). Brief exposure to 15°C to 30°C (59°F to 86°F) permitted (see USP Controlled Room...

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.