FDA

Voquezna

Approved 1 Nov 2023OralTablet

The FDA lists this product in 4 strengths and forms.

Indications

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 )

Contraindications

VOQUEZNA is contraindicated in patients with a known hypersensitivity to vonoprazan or any component of VOQUEZNA. Reactions have included anaphylactic shock [see Adverse Reactions (6.2) and Description (11) ] . VOQUEZNA is contraindicated with rilpivirine-containing products [see Drug Interactions (7) ] . For information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with VOQUEZNA, refer to the Contraindications section of the corresponding prescribing information.

Known hypersensitivity to vonoprazan or any component of VOQUEZNA. ( 4 ) Rilpivirine-containing products. ( 4 , 7 )

Warnings and precautions

Gastric Malignancy : Symptomatic response to treatment does not preclude the presence of gastric malignancy; consider additional follow-up and diagnostic testing. ( 5.1 ) Acute Tubulointerstitial Nephritis : Discontinue treatment and evaluate patients. ( 5.2 ) Clostridioides difficile -Associated Diarrhea (CDAD) : May be associated with an increased risk; use the shortest duration of treatment appropriate to the condition.

( 5.3 ) Bone Fracture, including Osteoporosis-related Fracture : Use the shortest duration of treatment appropriate to the condition. ( 5.4 ) Severe Cutaneous Adverse Reactions : Discontinue at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. ( 5.5 ) Vitamin B12 (Cobalamin) Deficiency : Long-term use may lead to malabsorption or deficiency; consider further workup if clinical symptoms are present.

At a glance

Brand name: Voquezna
Active substance: vonoprazan fumarate
Route: Oral
Dosage form: Tablet
Applicant: Phathom
Status: Prescription
FDA approval: 1 Nov 2023
Application: NDA215151-001

Indications

( 1 ) in combination with amoxicillin for the treatment of H. pylori infection in adults. ( 1 )

Contraindications

Known hypersensitivity to vonoprazan or any component of VOQUEZNA. ( 4 ) Rilpivirine-containing products. ( 4 , 7 )

Warnings and precautions

Interactions

Table 9 and Table 10 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with VOQUEZNA and instructions for preventing or managing them. 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) ] .

Consult the labeling of concomitantly used drugs to obtain further information about interactions with vonoprazan. Table 9: Drug Interactions Affecting Drugs Co-Administered with VOQUEZNA and Interactions with Diagnostics Drugs Dependent on Gastric pH for Absorption Antiretrovirals Clinical Effect Vonoprazan reduces intragastric acidity [see Clinical Pharmacology (12.2) ], which may alter the absorption of antiretroviral drugs, leading to changes in the safety and/or effectiveness.

Prevention or Management Rilpivirine-containing products Concomitant use with VOQUEZNA is contraindicated . Atazanavir Avoid concomitant use with VOQUEZNA. Nelfinavir Other antiretrovirals See the prescribing information of other antiretroviral drugs dependent on gastric pH for absorption prior to concomitant use with VOQUEZNA. Other Drugs (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) Clinical Effect Vonoprazan reduces intragastric acidity [see Clinical Pharmacology (12.2) ] , which may decrease the absorption of drugs reducing their effectiveness.

Prevention or Management See the prescribing information for other drugs dependent on gastric pH for absorption. Combination Therapy with Clarithromycin and/or Amoxicillin Clinical Effect Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and is contraindicated. Amoxicillin also has drug interactions. Prevention or Management See Contraindications and Warnings and Precautions in the prescribing information for clarithromycin.

See Drug Interactions in the prescribing information for amoxicillin. Certain CYP3A Substrates Where Minimal Concentration Changes May Lead to Serious Toxicities Clinical Effect Vonoprazan is a weak CYP3A inhibitor [see Clinical Pharmacology (12.3) ] . Vonoprazan may increase exposure of CYP3A4 substrates, which may increase the risk of adverse reactions related to these substrates. Prevention or Management Frequently monitor concentrations and/or adverse reactions related to the substrate drugs when used with VOQUEZNA.

Dosage reduction of substrate drugs may be needed. See prescribing information for the relevant substrate drugs. CYP2C19 Substrates (e.g., clopidogrel, citalopram, cilostazol) Clinical Effect Vonoprazan is a CYP2C19 inhibitor [see Clinical Pharmacology (12.3) ] . Vonoprazan may reduce plasma concentrations of the active metabolite of clopidogrel and may cause reduction in platelet inhibition. Vonoprazan may increase exposure of CYP2C19 substrate drugs (e.g., citalopram, cilostazol).

Prevention or Management Clopidogrel Carefully monitor the efficacy of clopidogrel and consider alternative anti-platelet therapy. Citalopram and Cilostazol Carefully monitor patients for adverse reactions associated with citalopram and cilostazol. See the prescribing information for dosage adjustments. Chromogranin Test for Neuroendocrine Tumors Clinical Effect Vonoprazan reduces intragastric acidity [see Clinical Pharmacology (12.2) ] , which increases CgA levels and may cause false positive results in diagnostic investigations for neuroendocrine tumors .

Prevention or Management Assess CgA levels at least 4 weeks after stopping VOQUEZNA treatment and repeat the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), use the same commercial laboratory for testing, as reference ranges between tests may vary. Interaction with Secretin Stimulation Test Clinical Effect Hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma.

Prevention or Management Temporarily stop VOQUEZNA at least 4 weeks before assessing to allow gastrin levels to return to normal [see Clinical Pharmacology (12.2) ] . Table 10: Drug Interactions Affecting VOQUEZNA When Co-Administered with Other Drugs Strong or Moderate CYP3A4 Inducers Clinical Effect Vonoprazan is a CYP3A substrate. Strong or moderate CYP3A inducers decrease vonoprazan exposure [see Clinical Pharmacology (12.3) ], which may reduce the effectiveness of VOQUEZNA.

Prevention or Management Avoid concomitant use with VOQUEZNA. See full prescribing information for a list of clinically important drug interactions. ( 7 )

Pregnancy and breastfeeding

8.1Pregnancy Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to VOQUEZNA during pregnancy. Healthcare providers are encouraged to register patients by calling 1-866-609-1612 or visiting https://voqueznapregnancyregistry.com/ . Risk Summary There are no adequate and well-controlled studies of vonoprazan in pregnant women. Available data from pharmacovigilance reports with vonoprazan-containing products used in pregnant women are not sufficient to evaluate for a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

In pregnant rats, no adverse effects were noted after oral administration of vonoprazan during organogenesis at approximately 27-times the maximum recommended human dose (MRHD), based on AUC exposure comparisons. In a pre- and postnatal development (PPND) study, pups from dams orally administered vonoprazan during organogenesis and through lactation exhibited liver discoloration, which, in follow-up mechanistic animal studies, was associated with necrosis, fibrosis, and hemorrhage at a dose approximately 22-times the MRHD, based on AUC comparisons that were likely attributable to exposure during lactation [see Use in Specific Populations (8.2) ] .

These effects were not observed at the next lower dose in this study, which was approximately equal to the MRHD, based on AUC comparison; however, they were seen at clinically relevant exposures in dose range-finding studies in rats (see Data) . The background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes.

In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Pregnant rats were orally administered vonoprazan at doses of 30, 100, or 300 mg/kg/day (7-, 27-, 130-times the MRHD based on AUC comparison at the same doses from unmated female rats from separate studies) during the period of organogenesis from gestation day (GD) 6 to 17.

During maternal dosing, one high-dose female died and decreased body weight and food consumption occurred at the middle and highest doses. No embryo-fetal lethality was observed but decreased fetal body weight was observed in the highest dose group. Fetal abnormalities were limited to the 300 mg/kg/day and included ventricular septal defect and mal-positioned subclavian artery in fetuses in a majority (15/19) of litters, as well as tail abnormalities and small anal opening.

No adverse embryo-fetal effects were observed at the 100 mg/kg/day. Pregnant rabbits were orally administered vonoprazan at doses of 3, 10, or 30 mg/kg/day (0.04-, 1.5-, 10-times the MRHD based on AUC comparison) during the period of organogenesis from GD 6 to 18. Two animals aborted at the highest dose and decreased body weight and food consumption occurred at the mid and high doses. No embryo-fetal mortality or toxicity occurred.

There were no external, visceral, or skeletal abnormalities. In a PPND study, pregnant female rats were orally administered vonoprazan at doses of 1, 3, 10, or 100 mg/kg/day (0.01-, 0.18-, 1.1-, 22-times the MRHD based on AUC comparison) from GD 6 to lactation day (LD) 21. Decreased body weight gain and food consumption were present in dams at the highest dose during lactation. Decreased body weight gain compared to controls was observed in the offspring from dams in the high dose group.

Liver discoloration occurred in offspring from the high dose group at LD 4 but was not present in animals examined after weaning. Similarly, in dose range-finding studies in rats and follow-up mechanistic animal studies, the liver discoloration was observed and characterized as necrosis, fibrosis, and hemorrhage at equal to or greater than clinically relevant exposures based on AUC comparisons. The mechanistic studies further demonstrated the effect was likely attributable to vonoprazan exposure during lactation [see Use in Specific Populations (8.2) ] .

The clinical relevance of the liver findings is uncertain. Exposure margins from vonoprazan between the animal and clinical studies for vonoprazan, amoxicillin, and clarithromycin used in combination may be lower due to increased vonoprazan exposure from concomitant use with clarithromycin in patients [see Clinical Pharmacology (12.3) ] .

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.

6.1Clinical 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 VOQUEZ

Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA

Voquezna

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Voquezna

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.1Presence of Gastric Malignancy

5.2Acute Tubulointerstitial Nephritis

5.4Bone Fracture

5.5Severe Cutaneous Adverse Reactions

5.6Vitamin B12 (Cobalamin) Deficiency

5.7Hypomagnesemia and Mineral Metabolism

5.8Interactions with Diagnostic Investigations for Neuroendocrine Tumors

5.9Fundic Gland Polyps Use of

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Pregnancy Exposure Registry

Adverse reactions

6.1Clinical Trials Experience

Composition

Strengths and forms

Official product information