Dosing & Uses
Dosage Forms & Strengths
tablet
- 10mg
- 20mg
Erosive Esophagitis
Treatment
- Indicated for healing of all grades of erosive esophagitis and relief of associated heartburn
- 20 mg PO qDay x 8 weeks
Maintenance
- Indicated to maintain healing of all grades of erosive esophagitis and relief of associated heartburn
- 10 mg PO qDay for up to 6 months
Helicobacter pylori infection
Indicated in combination with amoxicillin, or in combination with amoxicillin and clarithromycin for treatment of H pylori infection
Dual therapy
- Vonoprazan 20 mg BID plus amoxicillin 1,000 mg TID x 14 days
- Also available as copackaged product: Voquezna Dual Pak contains vonoprazan and amoxicillin
Triple therapy
- Vonoprazan 20 mg BID plus amoxicillin 1,000 mg TID plus clarithromycin 500 mg BID x 14 days
- Also available as copackaged product: Voquezna Triple Pak contains vonoprazan, amoxicillin, and clarithromycin
Dosage Modifications
Renal impairment
-
Healing of erosive esophagitis
- eGFR ≥30 mL/min: No dosage adjustment required
- eGFR <30 mL/min: Reduce dose to 10 mg PO qDay
-
Maintenance of healed erosive esophagitis
- All severities: No dosage adjustment required
-
Treatment of H pylori infection
- eGFR ≥30 mL/min: No dosage adjustment required
- eGFR <30 mL/min: Not recommended
Hepatic impairment
-
Healing of erosive esophagitis
- Mild (Child-Pugh A): No dosage adjustment required
- Moderate or severe (Child-Pugh B or C): Reduce dose to 10 mg PO qDay
-
Maintenance of healed erosive esophagitis
- All severities: No dosage adjustment required
-
Treatment of H pylori infection
- Mild (Child-Pugh A): No dosage adjustment required
- Moderate or severe (Child-Pugh B or C): Not recommended
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (1)
- rilpivirine
vonoprazan will decrease the level or effect of rilpivirine by inhibition of GI absorption. Applies only to oral form of both agents. Contraindicated.
Serious - Use Alternative (41)
- amobarbital
amobarbital will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- apalutamide
apalutamide will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- armodafinil
armodafinil will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- atazanavir
vonoprazan will decrease the level or effect of atazanavir by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- belzutifan
belzutifan will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- bexarotene
bexarotene will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- bosentan
bosentan will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- butabarbital
butabarbital will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- butalbital
butalbital will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- carbamazepine
carbamazepine will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- cenobamate
cenobamate will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- dabrafenib
dabrafenib will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- dasatinib
vonoprazan will decrease the level or effect of dasatinib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- efavirenz
efavirenz will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- elagolix
elagolix will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- encorafenib
encorafenib will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- enzalutamide
enzalutamide will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erlotinib
vonoprazan will decrease the level or effect of erlotinib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- etravirine
etravirine will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fosphenytoin
fosphenytoin will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ivosidenib
ivosidenib will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lorlatinib
lorlatinib will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lumacaftor/ivacaftor
lumacaftor/ivacaftor will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- mavacamten
mavacamten will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- mitapivat
mitapivat will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- mitotane
mitotane will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- modafinil
modafinil will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nafcillin
nafcillin will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nelfinavir
vonoprazan will decrease the level or effect of nelfinavir by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- pentobarbital
pentobarbital will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- pexidartinib
pexidartinib will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- phenobarbital
phenobarbital will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- phenytoin
phenytoin will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- primidone
primidone will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifabutin
rifabutin will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifampin
rifampin will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifapentine
rifapentine will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- secobarbital
secobarbital will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- sotorasib
sotorasib will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- St John's Wort
St John's Wort will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
Monitor Closely (42)
- alfentanil
vonoprazan will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- carbamazepine
vonoprazan will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- carbonyl iron
vonoprazan will decrease the level or effect of carbonyl iron by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
- cilostazol
vonoprazan will increase the level or effect of cilostazol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Reduce cilostazol dose to 50 mg BID when coadministered with strong or moderate inhibitors of CYP2C19.
- citalopram
vonoprazan will increase the level or effect of citalopram by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
- clonidine
vonoprazan will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- clopidogrel
vonoprazan will decrease the level or effect of clopidogrel by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Vonoprazan may reduce plasma concentrations of the active metabolite of clopidogrel and may cause reduction in platelet inhibition.
- colchicine
vonoprazan will increase the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- cyclosporine
vonoprazan will increase the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- dihydroergotamine
vonoprazan will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- disopyramide
vonoprazan will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- ergotamine
vonoprazan will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- ethosuximide
vonoprazan will increase the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- everolimus
vonoprazan will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- fentanyl
vonoprazan will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- ferric carboxymaltose
vonoprazan will decrease the level or effect of ferric carboxymaltose by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
- ferric citrate
vonoprazan will decrease the level or effect of ferric citrate by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
- ferric derisomaltose
vonoprazan will decrease the level or effect of ferric derisomaltose by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
- ferric gluconate
vonoprazan will decrease the level or effect of ferric gluconate by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
- ferric maltol
vonoprazan will decrease the level or effect of ferric maltol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
- ferric pyrophosphate DIALYSATE
vonoprazan will decrease the level or effect of ferric pyrophosphate DIALYSATE by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
- ferric pyrophosphate IV
vonoprazan will decrease the level or effect of ferric pyrophosphate IV by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
- ferrous fumarate
vonoprazan will decrease the level or effect of ferrous fumarate by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
- ferrous gluconate
vonoprazan will decrease the level or effect of ferrous gluconate by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
- ferrous sulfate
vonoprazan will decrease the level or effect of ferrous sulfate by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
- ferumoxytol
vonoprazan will decrease the level or effect of ferumoxytol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
- iron dextran complex
vonoprazan will decrease the level or effect of iron dextran complex by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
- iron sucrose
vonoprazan will decrease the level or effect of iron sucrose by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
- itraconazole
vonoprazan will decrease the level or effect of itraconazole by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Closely monitor for reduced itraconazole efficacy if combined. Itraconazole capsules only: Separate administration by at least 1 hr before or 2 hr after ketoconazole.
- ketoconazole
vonoprazan will decrease the level or effect of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Separate administration by at least 1 hr before or 2 hr after ketoconazole.
- midazolam
vonoprazan will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- mycophenolate
vonoprazan will decrease the level or effect of mycophenolate by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Enteric-coated mycophenolate sodium may be less sensitive to this interaction.
- pacritinib
vonoprazan will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- pimozide
vonoprazan will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- polysaccharide iron
vonoprazan will decrease the level or effect of polysaccharide iron by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
- quinidine
vonoprazan will increase the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- quinine
vonoprazan will increase the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- repaglinide
vonoprazan will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- sirolimus
vonoprazan will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- tacrolimus
vonoprazan will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- theophylline
vonoprazan will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
- triazolam
vonoprazan will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.
Minor (0)
Adverse Effects
1-10%
2-8 week erosive esophagitis healing phase
- Gastritis (3%)
- Diarrhea (2%)
- Abdominal distension (2%)
- Abdominal pain (2%)
- Nausea (2%)
24-week erosive esophagitis maintenance phase
- Gastritis (6%)
- Abdominal pain (4%)
- Dyspepsia (4%)
- Hypertension (3%)
- Urinary tract infection (3%)
H pylori treatment with antibiotics
- Diarrhea (4-5%)
- Dysgeusia (1-5%)
- Vulvovaginal candidiasis (2-3%)
- Abdominal pain (2-3%)
- Headache (1-3%)
- Hypertension (1-2%)
- Nasopharyngitis (1-2%)
Postmarketing Reports
Blood and lymphatic system disorders: Thrombocytopenia
Immune system disorders: Anaphylactic shock
Infections and infestations: C difficile (with concomitant antibacterials)
Investigation: Hypomagnesemia, hypokalemia, hypocalcemia, vitamin B12 deficiency
Hepatobiliary disorders: Hepatic injury, hepatic failure, jaundice
Skin and subcutaneous tissue disorders: Drug eruption, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
Warnings
Contraindications
Known hypersensitivity to vonoprazan or any component of drug product
Rilpivirine-containing products, owing to inhibition of gastric pH by vonoprazan
Contraindication involving use with clarithromycin and amoxicillin (see specific drug monographs)
Cautions
Acute tubulointerstitial nephritis reported; if suspected, discontinue drug and evaluate patient
Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) reported; discontinue drug at first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation
Long-term use of acid-suppressing drugs can lead to malabsorption of Vitamin B12 caused by hypo- or achlorhydria; vitamin B12 deficiency has been reported postmarketing with vonoprazan; consider further workup if clinical symptoms consistent with vitamin B12 deficiency observed
Presence of gastric malignancy
- Symptomatic response to vonoprazan does not preclude presence of gastric malignancy
- Consider additional follow-up and diagnostic testing in patients who have a suboptimal response or an early symptomatic relapse after completing treatment
- In older patients, also consider endoscopy
Closteridiodes difficile-associated diarrhea
- Proton pump inhibitors (PPIs) may be associated with increased risk of Clostridioides difficile-associated diarrhea (CDAD), especially in hospitalized patients
- Vonoprazan, another proton pump blocker that inhibits gastric acid production, may also increase CDAD risk
- Consider CDAD in patients with diarrhea that does not improve
- Use vonoprazan for shortest duration that is appropriate
Bone fracture
- PPIs may increase risk for osteoporosis-related hip, writs, or spine fractures
- Fracture risk was increased with high-dose, defined as multiple daily doses, and long-term therapy (≥1 year)
- Bone fracture, including osteoporosis-related fracture, has also been reported with vonoprazan
- Use vonoprazan for shortest duration that is appropriate
- Manage patients at risk for osteoporosis-related fractures according to established treatment guidelines
Hypomagnesemia and mineral metabolism
- Hypomagnesemia reported postmarketing
- Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients
- Consider monitoring magnesium levels before initiating and periodically in patients expected to be on prolonged treatment, those who are taking drugs that may have increased toxicity in the presence of hypomagnesemia (eg, digoxin), or drugs that may cause hypomagnesemia (eg, diuretics)
- Treatment of hypomagnesemia may require magnesium replacement and discontinuation of vonoprazan
- Consider monitoring magnesium and calcium levels before initiating and periodically while on treatment in patients with preexisting risk of hypocalcemia (eg, hypoparathyroidism)
- Supplement with magnesium and/or calcium, as necessary
- If hypocalcemia is refractory to treatment, consider discontinuing vonoprazan
Fundic gland polyps
- Use associated with risk of fundic gland polyps that increases with long-term use, especially ≥1 year
- Fundic gland polyps reported in clinical trials and postmarketing use with PPIs
- Most patients who developed fundic gland polyps were asymptomatic and the polyps were identified incidentally on endoscopy
- Use vonoprazan for shortest duration that is appropriate
Drug interaction overview
- Inhibitor of CYP2C19 and CYP3A (weak)
- Substrate of CYP3A4
-
Drugs dependent on gastric pH for absorption
- Contraindicated with rilpivirine
- Avoid or use caution with other drugs
- Vonoprazan reduces intragastric acidity which may decrease absorption of antiretroviral drugs (eg, rilpivirine, atazanavir) or other drugs (eg, iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) leading to changes in safety and/or effectiveness
-
Sensitive CYP3A substrates
- Increase monitoring and/or modify dose of sensitive CYP3A substrates
- Vonoprazan is a weak CYP3A inhibitor; may increase exposure of sensitive CYP3A4 substrates
-
CYP2C19 substrates
- Clopidogrel: Monitor efficacy/consider alternative anti-platelet therapy
- Citalopram, cilostazol: Monitor patients for adverse reactions; consider dose reduction
- Vonoprazan may reduce plasma concentrations of clopidogrel’s active metabolite and may cause reduction in platelet inhibition
- Vonoprazan may increase exposure of CYP2C19 substrate drugs (eg, citalopram, cilostazol)
-
Strong or moderate CYP3A4 inducers
- Avoid coadministration
- Strong or moderate CYP3A inducers decrease vonoprazan exposure, which may reduce efficacy
-
Chromogranin test for neuroendocrine tumors
- Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity
- Increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors
- Temporarily discontinue vonoprazan at least 14 days before assessing CgA levels and consider repeating test if initial CgA levels are high
- If serial tests are performed (eg, for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary
-
Secretin stimulation test
- May cause hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma
- Temporarily discontinue vonoprazan at least 14 days before assessing to allow gastrin levels to return to baseline
Pregnancy & Lactation
Pregnancy
Available data from pharmacovigilance reports with vonoprazan use in pregnant females are not sufficient to evaluate for drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes
Report pregnancies to the Phathom Pharmaceuticals, Inc. Adverse Event reporting line at 1-800-775- PHAT (7428)
Animal studies
- In pregnant rats, no adverse effects were noted after oral administration of vonoprazan during organogenesis at ~27-times the maximum recommended human dose (MRHD) based on AUC exposure comparisons
- Pups from dams orally administered vonoprazan during organogenesis and through lactation exhibited liver discoloration that was associated with necrosis, fibrosis, and hemorrhage at a dose ~22x the MRHD
Lactation
There are no data regarding the presence of vonoprazan in human milk, the effects on the breastfed infant or the effects on milk production
Vonoprazan and its metabolites are present in rat milk; liver injury occurred in offspring from pregnant and lactating rats administered oral vonoprazan at AUC exposures approximately equal to and greater than the MRHD
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Potassium-competitive acid blocker (PCAB)
Suppresses basal and stimulated gastric acid secretion at secretory surface of 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, as it blocks the final step of acid production
Does not require activation by acid; may selectively concentrate in parietal cells in both resting and stimulated states
Binds to active proton pumps in noncovalent and reversible manner
Absorption
Peak plasma time
- 10 mg/day: 1.5 hr
- 20 mg/day: 2 hr
- 20 mg BID: 3 hr
Peak plasma concentration
- 10 mg/day: 11.7 ng/mL
- 20 mg/day: 26.1 ng/mL
- 20 mg BID: 37.8 ng/mL
AUC
- 10 mg/day: 92.9 hr⋅ng/mL
- 20 mg/day: 230.9 hr⋅ng/mL
- 20 mg BID: 272.5 hr⋅ng/mL
Distribution
Protein bound: 85-88%
Vd
- 10 mg/day: 1,270 L
- 20 mg/day: 1,114 L
- 20 mg BID: 782.7 L
Metabolism
metabolized to inactive metabolites via multiple pathways by a combination of cytochrome P450 (CYP) isoforms (CYP3A4/5, CYP2B6, CYP2C19, CYP2C9 and CYP2D6) along with sulfo- and glucuronosyl-transferases
Elimination
Half-life
- 10 mg/day: 7.7 hr
- 20 mg/day: 7.9 hr
- 20 mg BID: 6.8 hr
Clearance
- 10 mg/day: 120.2 L/hr
- 20 mg/day: 100.2 L/hr
- 20 mg BID: 81.3 L/hr
Excretion
- Urine: 67% (8% unchanged)
- Feces: 31% (1.4% unchanged)
Pharmacogenomics
CYP2C19 polymorphisms have been evaluated in clinical studies and there were no considerable differences in pharmacokinetics of vonoprazan based on CYP2C19 metabolizer status
Administration
Oral Administration
May take with or without food
Swallow tablet whole; do not chew or crush
Missed dose
-
Healing or maintenance of erosive esophagitis
- Within 12 hr of missed dose: Take as soon as possible
- >12 hr of missed dose: Skip missed dose, and administer next dose at regularly scheduled time
- Continue with normal dosing schedule until medication is completed
-
H pylori infection
- Within 4 hr of missed dose: Take as soon as possible
- >4 hr of missed dose: Skip missed dose, and administer next dose at regularly scheduled time
- Continue with normal dosing schedule until medication is completed
Storage
- Store at controlled room temperature between 20-25ºC (68-77ºF); excursions permitted between 15-30ºC (59-86ºF)
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Formulary
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