Dosing & Uses
Dosage Forms & Strengths
copackaged tablets and capsules
- tablets: vonoprazan 20 mg
- capsules: amoxicillin 500 mg
- Carton contains 14 daily administration packs for twice daily dosing of vonoprazan and 3 times daily dosing of amoxicillin
Helicobacter pylori Infection
Not released on market since May 2022 FDA approval owing to the detection of trace levels of a nitrosamine impurity
Indicated for treatment of Helicobacter pylori (H pylori) infection
Dose: vonoprazan 20 mg PO BID plus amoxicillin 1000 mg PO TID x 14 days
Dosage Modifications
Renal impairment
- Mild-to-moderate (eGFR 30-89 mL/min): No dosage adjustment required
- Severe (eGFR <30 mL/min): Avoid
Hepatic impairment
- Mild (Child-Pugh A): No dosage adjustment required
- Moderate-to-severe (Child-Pugh B-C): Avoid
Dosing Considerations
Preventing bacterial resistance
- To reduce the development of drug-resistant bacteria and maintain the effectiveness, use only to treat or prevent infections that are proved or strongly suspected to be caused by susceptible bacteria
- Consider selecting or modifying therapy when culture and susceptibility information are available; if this information is unavailable, base empiric therapy on local epidemiology and susceptibility patterns
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (13)
- BCG vaccine live
amoxicillin decreases effects of BCG vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until Abx Tx complete to administer live bacterial vaccine.
- cholera vaccine
amoxicillin, cholera vaccine. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid coadministration of cholera vaccine with systemic antibiotics since these agents may be active against the vaccine strain. Do not administer cholera vaccine to patients who have received oral or parenteral antibiotics within 14 days prior to vaccination.
- demeclocycline
demeclocycline decreases effects of amoxicillin by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline.
- doxycycline
doxycycline decreases effects of amoxicillin by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline.
- eravacycline
eravacycline decreases effects of amoxicillin by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline.
- minocycline
minocycline decreases effects of amoxicillin by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline.
- mycophenolate
amoxicillin will decrease the level or effect of mycophenolate by Other (see comment). Avoid or Use Alternate Drug. Effect may be due to impairment of enterohepatic recirculation
- omadacycline
omadacycline decreases effects of amoxicillin by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline.
- pexidartinib
amoxicillin and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.
- pretomanid
amoxicillin, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.
- sarecycline
sarecycline decreases effects of amoxicillin by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline.
- tetracycline
tetracycline decreases effects of amoxicillin by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline.
- typhoid vaccine live
amoxicillin decreases effects of typhoid vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until Abx Tx complete to administer live bacterial vaccine.
Monitor Closely (26)
- acyclovir
amoxicillin, acyclovir. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.
- allopurinol
allopurinol decreases toxicity of amoxicillin by Other (see comment). Use Caution/Monitor. Comment: Allopurinol may increase potential for allergic or hypersensitivity reactions to amoxicillin.
- aspirin
amoxicillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
amoxicillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor. - aspirin rectal
amoxicillin, aspirin rectal. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.
amoxicillin, aspirin rectal. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor. - aspirin/citric acid/sodium bicarbonate
amoxicillin, aspirin/citric acid/sodium bicarbonate. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.
amoxicillin, aspirin/citric acid/sodium bicarbonate. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor. - bazedoxifene/conjugated estrogens
amoxicillin will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- bendroflumethiazide
amoxicillin, bendroflumethiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.
- chlorothiazide
amoxicillin, chlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.
- choline magnesium trisalicylate
amoxicillin, choline magnesium trisalicylate. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.
amoxicillin, choline magnesium trisalicylate. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor. - cyclopenthiazide
amoxicillin, cyclopenthiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.
- dienogest/estradiol valerate
amoxicillin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.
- estradiol
amoxicillin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- ethinylestradiol
amoxicillin will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.
- hydrochlorothiazide
amoxicillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.
- levonorgestrel oral/ethinylestradiol/ferrous bisglycinate
amoxicillin will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.
- mestranol
amoxicillin will decrease the level or effect of mestranol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- methotrexate
amoxicillin increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. Increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with concurrent administration of high or low doses of methotrexate and penicillins.
- methyclothiazide
amoxicillin, methyclothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.
- metolazone
amoxicillin, metolazone. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.
- rose hips
amoxicillin, rose hips. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.
- salicylates (non-asa)
amoxicillin, salicylates (non-asa). Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
- salsalate
amoxicillin, salsalate. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
- sodium phenylacetate
amoxicillin, sodium phenylacetate. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.
- sodium picosulfate/magnesium oxide/anhydrous citric acid
amoxicillin decreases effects of sodium picosulfate/magnesium oxide/anhydrous citric acid by altering metabolism. Use Caution/Monitor. Coadministration with antibiotics decreases efficacy by altering colonic bacterial flora needed to convert sodium picosulfate to active drug.
- sulfasalazine
amoxicillin, sulfasalazine. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
amoxicillin, sulfasalazine. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor. - willow bark
amoxicillin, willow bark. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.
Minor (10)
- amiloride
amiloride decreases levels of amoxicillin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Administer each drug at least 2 hours apart from each other; monitor for reduced antibiotic efficacy.
- azithromycin
azithromycin decreases effects of amoxicillin by pharmacodynamic antagonism. Minor/Significance Unknown.
- aztreonam
aztreonam, amoxicillin. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Combination may be used synergistically against Enterobacteriaceae.
- chloramphenicol
chloramphenicol decreases effects of amoxicillin by pharmacodynamic antagonism. Minor/Significance Unknown.
- clarithromycin
clarithromycin decreases effects of amoxicillin by pharmacodynamic antagonism. Minor/Significance Unknown.
- erythromycin base
erythromycin base decreases effects of amoxicillin by pharmacodynamic antagonism. Minor/Significance Unknown.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate decreases effects of amoxicillin by pharmacodynamic antagonism. Minor/Significance Unknown.
- erythromycin lactobionate
erythromycin lactobionate decreases effects of amoxicillin by pharmacodynamic antagonism. Minor/Significance Unknown.
- erythromycin stearate
erythromycin stearate decreases effects of amoxicillin by pharmacodynamic antagonism. Minor/Significance Unknown.
- pyridoxine (Antidote)
amoxicillin will decrease the level or effect of pyridoxine (Antidote) by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
Adverse Effects
1-10%
Diarrhea (5.2%)
Abdominal pain (2.6%)
Vulvovaginal candidiasis (2%)
Nasopharyngitis (2%)
Headache (1.4%)
Hypertension (1.1%)
<2%
- Blood and lymphatic system disorders: Anemia, leukocytosis, leukopenia, neutropenia
- Cardiac disorders: QT prolongation, tachycardia
- Eye disorders: Orbital edema
- Gastrointestinal disorders: Abdominal distention, 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: Liver function test abnormal
- 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
<1%
Dysgeusia (0.6%)
Postmarketing Reports
Vonoprazan
- Immune system disorders: Anaphylactic shock, urticaria, drug eruption
- Hepatobiliary disorders: Hepatic injury, hepatic failure, jaundice
- Skin and subcutaneous tissue disorders: Erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)
Amoxicillin
- Infections and infestations: Mucocutaneous candidiasis
- Gastrointestinal: Black hairy tongue, and hemorrhagic/pseudomembranous colitis; onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment
- Hypersensitivity reactions: Anaphylaxis, serum sickness–like reactions, erythematous maculopapular rashes, erythema multiforme, exfoliative dermatitis, hypersensitivity vasculitis, and urticaria
- Renal: Crystalluria
- Hemic and lymphatic systems: Hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, and agranulocytosis; 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
- Miscellaneous: Tooth discoloration (brown, yellow, or gray staining) reported; most occurred in pediatric patients; discoloration reduced or eliminated with brushing or dental cleaning in most cases
- Skin and subcutaneous tissue disorders: TEN, SJS, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP)
Warnings
Contraindications
Known hypersensitivity to any component – vonoprazan, or amoxicillin (or other beta-lactam antibacterials [eg, penicillins, cephalosporins])
Rilpivirine-containing products, owing to inhibition of gastric pH by vonoprazan
Cautions
Serious and occasionally fatal hypersensitivity reactions (eg, anaphylaxis, anaphylactic shock, rash, erythema multiforme, and Henoch-Schonlein purpura) reported with components; discontinue immediately and institute appropriate treatment if hypersensitivity occurs
Severe cutaneous adverse reactions (SCAR), including SJS and TEN, reported with all components; additionally, DRESS and AGEP have been reported with amoxicillin; discontinue at first signs of SCAR
Clostridioides difficile–associated diarrhea (CDAD) reported with acid-suppressing therapies and nearly all antibacterial agents; CDAD must be considered in all patients who present with diarrhea following antibacterial use; careful medical history necessary since CDAD reported to occur over 2 months after administration of antibacterial agents; if CDAD confirmed, discontinue, and implement appropriate management
High percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash; avoid in patients with mononucleosis
Prescribing this regimen in absence of proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit and increases risk for drug-resistant bacteria
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; assess CgA levels at least 14 days after treatment, and consider repeating test if initial CgA levels are high
Glucose tests: High urine concentrations of amoxicillin may cause false-positive results when using glucose tests based on the Benedict copper reduction reaction that determines the amount of reducing substances, like glucose, in the urine; use enzymatic glucose oxidase reactions instead while taking amoxicillin
Drug interaction overview
- Vonoprazan: CYP3A substrate; weak CYP3A inhibitor; CYP2C19 inhibitor
-
Strong or moderate CYP3A inducers
- Avoid coadministration
- Strong or moderate CYP3A inducers may decrease exposure of vonoprazan, which may reduce effectiveness
-
Probenecid
- Closely monitor
- Amoxicillin undergoes tubular secretion; probenecid may increase amoxicillin systemic exposure by blocking renal tubular secretion, which may increase risk of adverse reactions
-
Allopurinol
- Discontinue if skin rash occurs
- Increase incidence of rashes reported with coadministration of allopurinol and amoxicillin
-
Drugs dependent on gastric pH for absorption
- Rilpivirine: Contraindicated
- Atazanavir, nelfinavir: Avoid
- Other antiretroviral drugs: See prescribing for reliance on gastric pH for absorption
- Other drugs (eg, iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole, itraconazole); Check prescribing information for modifying time of dosage or avoidance
- Vonoprazan reduces intragastric acidity, which may alter absorption of certain drugs
-
Sensitive CYP3A4 substrates
- See prescribing information for sensitive CYP3A substrates
- Tacrolimus, cyclosporine: Dosage modification (dose reduction) may be needed; monitor closely
- Vonoprazan (a weak CYP3A inhibitor) may increase exposure of CYP3A4 substrates, which may increase risk of adverse reactions related to these substrates
-
CYP2C19 substrates
- Clopidogrel: Carefully monitor the efficacy of clopidogrel, and consider alternative anti-platelet therapy
- Citaprolam, cilostazol: Carefully monitor for adverse reactions
- Vonoprazan is a CYP2C19 inhibitor; may reduce plasma concentration of the active metabolite of clopidogrel, resulting in reduced platelet inhibition; may increase exposure of CYP2C19 substrate drugs
-
Oral anticoagulants
- Monitor INR, and adjust dose accordingly
- Abnormal prolongation of prothrombin time (increased INR) reported in patients receiving amoxicillin and oral anticoagulants
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
- Vonoprazan: 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 maximum recommended human dose (MRHD)
- Amoxicillin: No evidence of harm to the fetus found
Lactation
Vonoprazan
- 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
Amoxicillin
- Data from published clinical lactation study indicate that amoxicillin is present in human milk
- There are no data on the effects of amoxicillin on milk production
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
Vonoprazan
- 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
Amoxicillin
- Ampicillin derivative; elicits antibacterial effect by binding to penicillin-binding proteins and inhibiting biosynthesis of cell wall
Pharmacokinetics
Vonoprazan
-
Absorption
- Onset of antisecretory activity: 2-3 hr; elevated intragastric pH maintained for >24 hr
- Steady-state achieved: 3-4 days
- Peak plasma time: 2.5 hr (single-dose); 3 hr (steady-state)
- Peak plasma concentration: 25.2 ng/mL (single-dose); 37.8 ng/mL (steady-state)
- AUC: 154.8 nghr/mL (single-dose); 272.5 nghr/mL (steady-state)
-
Distribution
- Vd: 1001 L (single-dose); 782.7 L (steady-state)
- Protein bound: 85-88%
-
Metabolism
- Metabolized to inactive metabolites via multiple pathways by combination of CYP450 isoforms (CYP3A4/5, CYP2B6, CYP2C19, CYP2C9 and CYP2D6) along with sulfo- and glucuronosyl-transferases
-
Elimination
- Half-life: 7.1 hr (single-dose); 6.8 hr (steady-state)
- Clearance: 97.3 L/hr (single-dose); 81.3 L/hr (steady-state)
- Excretion: 67% urine (8% unchanged); 31% feces (1.4% unchanged)
Amoxicillin
- Half-life: 1.02 hr
- Absorption: 74-92%
- Distribution: Most body fluids and bone, CSF <1%
- Peak plasma time: 1-2 hr
- Protein bound: 17-20%
- Metabolism: Hepatic
- Excretion: Urine (60%)
Administration
Oral Administration
May take with or without food
Missed dose
- 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 20-25ºC (68-77ºF); brief exposure to 15-30ºC (59-86ºF) permitted
Protect from light
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