Acronyms
- ACG - American College of Gastroenterology
- AGA - American Gastroenterology Association
- BE - Barrett's esophagus
- EE - Erosive esophagitis
- GERD - Gastroesophageal reflux disease
- H2RA - Histamine-2-receptor antagonists (e.g. Pepcid)
- ODT - Orally disintegrating tablet
- OTC - Over-the-counter
- P = Drugs with pediatric dosing
- P-CAB - Potassium-competitive acid blockers
- PPI - Proton pump inhibitor
PREVALENCE
- The worldwide prevalence of GERD among adults is approximately 13.3%, and in developed nations, 10 - 20% of people report symptoms of heartburn or regurgitation at least once weekly. In the U.S., GERD is the number one gastrointestinal complaint seen in outpatient clinics. GERD increases with age, with 14% of adults less than 50 years being affected and 17.3% of those over 50 reporting symptoms. [4,5]
PATHOLOGY
- GERD occurs when stomach acid rises above the gastroesophageal junction and comes in contact with the esophagus. The lower esophageal sphincter protects the esophagus from stomach acid by contracting and closing the junction between the two structures. The sphincter relaxes under the following conditions : (1) to allow passage of food during eating, (2) in response to gastric distension to facilitate the release of gas (belching). GERD can happen if the sphincter does not close properly and/or relaxation is prolonged. Other conditions, including delayed gastric emptying and esophageal body dysfunction, can also contribute to GERD.
- The main symptoms of GERD are heartburn and regurgitation of food or acid [4,5]
RISK FACTORS
- Obesity and overweight - increases intra-abdominal pressure
- Hiatal hernia
- Tobacco products/smoking
- Family history
- Delayed gastric emptying
- Impaired esophageal peristalsis
- Bariatric surgery - gastric sleeve (sleeve gastrectomy) increases the risk for GERD and gastric bypass (RYGB) is a treatment for GERD (see weight loss procedures for more)
- Intragastric balloon
- Pregnancy - increases intra-abdominal pressure [4,5]
SYMPTOMS
- Classic symptoms
- Classic symptoms of GERD include the following:
- Heartburn - substernal burning sensation rising from the epigastrium up toward the neck
- Regurgitation - effortless return of gastric contents upward toward the mouth, often accompanied by an acid or bitter taste
- Symptoms may be worse after eating and/or at night when lying down [1]
- Alarm symptoms
- Alarm symptoms may indicate that something more concerning than GERD is causing the patient's complaints
- Alarm symptoms include the following:
- Dysphagia (difficulty swallowing)
- Odynophagia (painful swallowing)
- Weight loss
- Hematemesis
- GI bleeding
- Vomiting
- Anemia [1]
- Extraesophageal symptoms
- A number of symptoms involving the pharynx, larynx, and lungs have been attributed to GERD, and while GERD may play a role in these conditions, other etiologies must be ruled out before GERD is implicated. Examples of extraesophageal GERD symptoms include the following:
- Chronic cough
- Throat-clearing
- Hoarseness
- Globus sensation (sensation of a lump in throat)
- Laryngitis
- Asthma [1]
BARRETT'S ESOPHAGUS
- Overview
- Barrett's esophagus (BE) is metaplastic change of the distal esophagus, whereby the normal squamous epithelium is replaced by specialized columnar epithelium with goblet cells. Barrett's esophagus is a precursor to esophageal adenocarcinoma, and it is staged in the following manner:
- Non-dysplastic BE - metaplasia without dysplasia; rarely progresses to cancer (0.39%/year); endoscopic surveillance is recommended
- BE with low-grade dysplasia - annual risk for progression to cancer is 1 - 3%; surveillance is recommended and treatment may be appropriate in some patients
- BE with high-grade dysplasia - annual risk for progression to cancer is 5 - 10%; treatment is recommended
- Risk factors for Barrett's esophagus include:
- Chronic GERD
- Male sex
- Age > 50 years
- White race
- Tobacco smoking
- Obesity
- First-degree relative with Barrett's esophagus or esophageal adenocarcinoma [2,3]
- Treatment
- Treatment recommendations from the ACG are available here - ACG 2022 Guidelines on Barrett's Esophagus
DIAGNOSIS (ACG 2021 RECOMMENDATIONS)
- Patients with classic symptoms (heartburn, regurgitation) and no alarm symptoms
- Prescribe an 8-week trial of empiric PPIs once daily before a meal
- If symptoms resolve, attempt to discontinue PPI after 8 weeks
- If symptoms do not resolve or return after PPI discontinuation, endoscopy is recommended
- Patients with alarm symptoms or multiple risk factors for Barrett's esophagus
- Endoscopy is recommended
- Other
- Barium swallow is not recommended as a diagnostic test for GERD
- In patients for whom the diagnosis of GERD is suspected but not clear, and endoscopy shows no objective evidence of GERD, reflux monitoring off therapy is recommended to establish the diagnosis
- In patients who have chest pain without heartburn and who have had adequate evaluation to exclude heart disease, objective testing for GERD (endoscopy and/or reflux monitoring) is recommended [1]
TREATMENT (ACG 2021 RECOMMENDATIONS)
- Behavioral therapy
- Weight loss in overweight and obese patients
- Avoiding meals within 2 - 3 hours of bedtime
- Avoidance of tobacco products/smoking
- Avoidance of "trigger foods" such as coffee, chocolate, carbonated beverages, spicy foods, acidic foods such as citrus and tomatoes, and foods with high-fat content
- For patients with nighttime GERD symptoms, elevating the head of the bed
- Acid-suppressing medications
- PPIs are recommended over H2RAs (e.g. Pepcid)
- PPIs should be administered 30 - 60 minutes before a meal rather than at bedtime
- Patients with GERD (without Barrett's esophagus or erosive esophagitis) whose symptoms resolved with PPI therapy should attempt to discontinue their PPI and switch to on-demand therapy
- Patients with GERD who require maintenance PPI therapy should use the lowest effective PPI dose
- Other medications
- Prokinetic agents are not recommended unless there is objective evidence of gastroparesis
- Sucralfate is not recommended except during pregnancy
- Baclofen is not recommended
- Refractory GERD
- Patients with GERD that is refractory to PPI therapy should have further evaluation, which may include endoscopy and/or esophageal pH monitoring
- Switching to another PPI may be tried, but more than one switch is not supported
- Increasing PPI therapy to twice-daily dosing (before breakfast and dinner) has been shown to be effective in some studies and may be tried [1]
- Extraesophageal symptoms
- Patients with extraesophageal GERD symptoms should have a detailed medical history to look for non-GERD etiologies. If a non-GERD etiology seems likely and/or the patient does not have typical GERD symptoms (heartburn, regurgitation), further evaluation for non-GERD causes should be performed.
- For patients with typical (heartburn, regurgitation) and extraesophageal GERD symptoms, an 8 - 12 week trial of twice-daily PPI therapy may be tried before additional testing
- Patients with extraesophageal GERD symptoms who do not have typical GERD symptoms (heartburn, regurgitation) should undergo reflux testing before PPI therapy is tried [1]
PROTON PUMP INHIBITORS (PPIs)
- Overview
- PPIs are some of the most widely consumed medications in the world, and they have largely replaced H2RAs (e.g. Pepcid) as the preferred treatment for GERD. PPIs work by inhibiting the H+/K+ ATPase enzyme system (also called proton pumps) on the secretory surface of gastric parietal cells. PPIs only bind pumps that are actively secreting acid, so they are best given 30 - 60 minutes before a meal because food stimulates proton pump activity.
| Proton pump inhibitors |
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Dexlansoprazole (Dexilant®)
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Esomeprazole (Nexium®)
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Lansoprazole (Prevacid®)
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Omeprazole (Prilosec®)
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Omeprazole + sodium bicarbonate (Konvomep®)
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Omeprazole + sodium bicarbonate (Zegerid®)
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Pantoprazole (Protonix®)
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Rabeprazole (Aciphex®)
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- H. pylori treatment
- See PPI dosing for H. pylori treatment and prepackaged H. pylori treatments for more
- Side effects
- PPIs are generally well tolerated, and in trials, side effect profiles are comparable to placebo, with only diarrhea occurring at an incidence of 2 - 4% more than placebo.
- Drug interactions
- NOTE: The drug interactions presented here are NOT all-inclusive. Other interactions may exist. Drug interaction checkers provide the most efficient and practical way to check for interactions among multiple medications. A free interaction checker is available from Drugs.com (see Drugs.com interactions checker).
- Clopidogrel (Plavix®) - omeprazole and esomeprazole inhibit CYP2C19, which can prevent the conversion of clopidogrel to its active metabolite and reduce its antiplatelet activity. Patients taking clopidogrel who require a PPI should avoid omeprazole and esomeprazole. See clopidogrel and PPIs for more.
- HIV antiretrovirals - PPIs decrease exposure to some antiretrovirals (e.g. rilpivirine atazanavir, nelfinavir) and increase exposure to others (e.g. saquinavir). Patients on HIV antiretrovirals should consult with their healthcare provider for recommendations on taking a PPI. Rilpivirine and nelfinavir should not be taken with a PPI.
- Warfarin - PPIs may increase prothrombin time (PT) and INR in patients receiving warfarin. Monitor PT/INR closely when combining.
- Methotrexate - PPIs may increase exposure to methotrexate, particularly high-dose methotrexate. Monitor patients for toxicity during concomitant therapy and discontinue PPI if necessary.
- Digoxin - PPIs may increase exposure to digoxin. Monitor digoxin levels closely when combining.
- Mycophenolate mofetil - increased gastric pH may decrease the solubility of mycophenolate mofetil (Cellcept®) and prevent its conversion to mycophenolic acid, the active metabolite. Use caution when combining mycophenolate mofetil (Cellcept®) with PPIs. Another mycophenolate product, Myfortic®, contains the active moiety mycophenolic acid and does not appear to be affected by PPIs.
- Drugs dependent on gastric pH for absorption - drugs whose absorption is affected by gastric pH may have reduced exposure when taken with PPIs. Examples include iron salts, erlotinib, dasatinib, nilotinib, ketoconazole, and itraconazole.
- Tacrolimus - dexlansoprazole, omeprazole, esomeprazole, lansoprazole, and rabeprazole may increase tacrolimus exposure, especially in patients who are intermediate or poor metabolizers of CYP2C19. Monitor tacrolimus levels when combining.
- CYP2C19 substrates - omeprazole and esomeprazole are CYP2C19 inhibitors and may increase CYP2C19 substrate exposure
- CYP2C19 inhibitors and inducers - dexlansoprazole, omeprazole, esomeprazole, and lansoprazole are CYP2C19 sensitive substrates. CYP2C19 inducers may decrease exposure, and CYP2C19 inhibitors may increase exposure.
- CYP3A4 inhibitors and inducers - dexlansoprazole, omeprazole, esomeprazole, and lansoprazole are CYP3A4 sensitive substrates. CYP3A4 inducers may decrease exposure, and CYP3A4 inhibitors may increase exposure.
- False-positive urine THC test
- All PPIs state that there have been reports of false-positive urine THC tests in patients receiving PPIs, particularly pantoprazole. Several small studies that evaluated this phenomenon did not find it to be true. [PMID 31566030, PMID 29126183]
- Long-term effects / Precautions
- A number of observational studies have looked at the association between long-term PPI use and adverse outcomes. These studies have had mixed results, and a causal link cannot be established in most cases. The ACG makes the following statement about the risks of long-term PPI use:
- "PPIs are the most effective medical treatment for GERD. Some medical studies have identified an association between the long-term use of PPIs and the development of numerous adverse conditions including intestinal infections, pneumonia, stomach cancer, osteoporosis-related bone fractures, chronic kidney disease, deficiencies of certain vitamins and minerals, heart attacks, strokes, dementia, and early death. Those studies have flaws, are not considered definitive, and do not establish a cause-and-effect relationship between PPIs and the adverse conditions. High-quality studies have found that PPIs do not significantly increase the risk of any of these conditions except intestinal infections. Nevertheless, we cannot exclude the possibility that PPIs might confer a small increase in the risk of developing these adverse conditions. For the treatment of GERD, gastroenterologists generally agree that the well-established benefits of PPIs far outweigh their theoretical risks."
- Clostridium difficile-associated diarrhea
- Theoretically, reduced gastric acid may enable the survival of ingested C. difficile vegetative forms. Some observational studies have found an association between long-term PPI use and an increased risk of Clostridium difficile-associated diarrhea, while others have not.
- Osteoporosis and bone fractures
- Theoretically, reduced gastric acid secretion may cause calcium malabsorption and increase the risk of osteoporosis-related bone fractures. Some observational studies have found an association between long-term PPI use and bone fractures, while others have not.
- ACG 2021 recommendation
- For patients with GERD on PPIs who have no other risk factors for bone disease, we do not recommend that they raise their intake of calcium or vitamin D or that they have routine monitoring of bone mineral density
- Serious cutaneous reactions
- Rare cases of severe cutaneous reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in patients receiving PPIs.
- Cutaneous and systemic lupus erythematosus
- Cases of cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients receiving PPIs. Some episodes were new-onset disease, while others were exacerbations of existing disease. The majority of PPI-induced lupus erythematosus cases were cutaneous disease.
- CLE can occur at any time during PPI therapy, and patients of all ages have been affected. SLE can also happen at any time, and it is usually seen in adults (see drug-induced lupus for more).
- Most cases of PPI-induced lupus resolve within 4 - 12 weeks of drug discontinuation
- Vitamin B12 deficiency
- Chronic PPI therapy (> 3 years) may cause malabsorption of vitamin B12 through reduced gastric acid secretion
- ACG 2021 recommendation
- For patients with GERD on PPIs who have no other risk factors for vitamin B12 deficiency, we do not recommend that they raise their intake of vitamin B12 or that they have routine monitoring of serum B12 levels
- Hypomagnesemia
- Chronic PPI therapy (> 3 months, but typically > 1 year) has been associated with rare cases of hypomagnesemia, which can cause or worsen hypocalcemia and/or hypokalemia. Patients receiving concomitant diuretics may be at greater risk. Use caution in patients receiving digoxin because hypomagnesemia can increase the risk of digoxin toxicity (e.g., heart block, arrhythmias).
- ACG 2021 recommendation
- There are insufficient data to make a meaningful recommendation regarding the need for monitoring magnesium levels in patients on chronic PPI therapy
- FDA 2011 recommendation
- Healthcare professionals should consider obtaining serum magnesium levels prior to initiation of prescription PPI treatment in patients expected to be on these drugs for long periods of time, as well as patients who take PPIs with medications such as digoxin, diuretics, or drugs that may cause hypomagnesemia. For patients taking digoxin, a heart medicine, this is especially important because low magnesium can increase the likelihood of serious side effects. Healthcare professionals should consider obtaining magnesium levels periodically in these patients. [FDA PPI communication]
- Interactions with diagnostic investigations for neuroendocrine tumors
- Serum chromogranin A (CgA), a biomarker used to diagnose neuroendocrine tumors, is elevated by acid-reducing drugs. CgA testing in patients receiving PPIs can cause false-positive results. Stop PPIs at least 14 days before checking serum CgA levels, and consider repeating the test if results are elevated.
- Fundic gland polyps
- Fundic gland polyps have been reported in patients receing PPIs, especially with long-term use (> 1 year). Most polyps were asymptomatic and discovered incidentally on endoscopy.
- Kidney disease
- Cases of acute tubulointerstitial nephritis have been reported in patients receiving PPIs. Some observational studies have found an association between long-term PPI use and chronic kidney disease, while others have not.
- PPI manufacturers do not recommend dose adjustments for people with any degree of renal impairment
- ACG 2021 recommendation
- For patients with GERD on PPIs who have no other risk factors for kidney disease, we do not recommend that they have routine monitoring of serum creatinine levels
- PPIs can be used to treat GERD in patients with renal insufficiency with close monitoring of renal function or consultation with a nephrologist
- Liver disease
- Dexlansoprazole (Dexilant®)
- Child-Pugh A: no dose adjustment necessary
- Child-Pugh B: maximum dose is 30 mg once daily
- Child-Pugh C: not recommended
- Esomeprazole (Nexium®)
- Child-Pugh A/B: no dose adjustment necessary
- Child-Pugh C: exposure is increased. Dose reduction is recommended.
- Lansoprazole (Prevacid®)
- Child-Pugh A/B: no dose adjustment necessary
- Child-Pugh C: maximum dose is 15 mg once daily
- Omeprazole (Prilosec®)
- Liver disease: exposure is increased. Consider dose reduction.
- Pantoprazole (Protonix®)
- Liver disease: no dose adjustment necessary for any degree of liver disease
- Rabeprazole (Aciphex®)
- Child-Pugh A/B: no dose adjustment necessary
- Child-Pugh C: has not been studied. Not recommended.
DISCONTINUING PPIs (AGA 2022 RECOMMENDATIONS)
- Overview
- In 2022, the AGA published guidelines on who can safely discontinue PPIs and how it should be done. Those recommendations are outlined below.
- Patients who should not discontinue PPIs
- Patients with a history of any of the following:
- Severe erosive esophagitis
- Esophageal ulcer
- Peptic stricture
- Barrett's esophagus
- Eosinophilic esophagitis
- Zollinger-Ellison syndrome
- Idiopathic pulmonary fibrosis
- Patients at high risk for upper GI bleeding. High risk is defined as any of the following:
- History of upper GI bleeding
- Taking multiple antithrombotics (including both anticoagulants and antiplatelets agents)
- Taking aspirin or an NSAID with an additional risk factor for upper GI bleeding (e.g. older than 60 years, severe medical comorbidity, using second NSAID or aspirin, taking an antithrombotic, or taking an oral corticosteroid)
- Patients who can consider discontinuing PPIs
- Patients with no definitive indication for PPI therapy (see above)
- The decision to discontinue PPIs should be based solely on the lack of an indication for PPI use, and not because of concern for PPI-associated adverse events.The presence of a PPI-associated adverse events or a history of a PPI-associated adverse events in a current PPI user is not an independent indication for PPI withdrawal. Similarly, the presence of underlying risk factors for the development of an adverse event associated with PPI use should also not be an independent indication for PPI withdrawal.
- Discontinuation regimens
- Patients who discontinue long-term PPI therapy should be advised that they may develop transient upper gastrointestinal symptoms due to rebound acid hypersecretion
- When deprescribing PPIs, either dose tapering or abrupt discontinuation can be considered. One small study (N=97) found no difference between abrupt discontinuation and a 3-week taper. [PMID 16948806] [6]
VONOPRAZAN (VOQUEZNA)
- Mechanism
- Vonoprazan (Voquezna®), approved in 2023, is part of a new class of acid-reducing drugs, also referred to as potassium-competitive acid blockers (P-CABs), that work by competing with potassium ions at gastric H+/K+-ATPase proton pumps; this differs from traditional PPIs that inhibit the pump through covalent binding. Proposed advantages of vonoprazan over PPIs include: (1) longer half-life (9 hours vs 1 - 2 hours); (2) acid stable, which gives it a more rapid onset of action; and (3) food-independent effects. [7]
- FDA-approved indications
- Erosive esophagitis - healing and maintaining healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults
- Heartburn - relief of heartburn associated with non-erosive GERD in adults
- H. pylori treatment - in combination with amoxicillin or amoxicillin + clarithromycin in adults
- Dosage form
- Voquezna® tablet
- 10 mg
- 20 mg
- No generic / $$$$
- Voquezna® DualPak
- Vonoprazan 20 mg (28 tablets)
- Amoxicillin 500 mg (84 capsules)
- No generic / $$$$
- Voquezna® TriplePak
- Vonoprazan 20 mg (28 tablets)
- Amoxicillin 500 mg (56 capsules)
- Clarithromycin 500 mg (28 tablets)
- No generic / $$$$
- Dosing
- Healing of erosive esophagitis
- 20 mg once daily for 8 weeks
- Maintenance of healed erosive esophagitis
- 10 mg once daily for up to 6 months
- Relief of heartburn associated with non-erosive GERD
- 10 mg once daily for 4 weeks
- H. pylori infection
- Triple Therapy: Vonoprazan 20 mg plus amoxicillin 1,000 mg plus clarithromycin 500 mg, each given twice daily (in the morning and evening, 12 hours apart) for 14 days
- Dual Therapy: Vonoprazan 20 mg given twice daily (in the morning and evening) plus amoxicillin 1,000 mg three times daily (in the morning, mid-day, and evening) for 14 days [8]
- Kidney disease
- Healing of erosive esophagitis
- CrCL ≥ 30 ml/min: 20 mg once daily
- CrCL < 30 ml/min: 10 mg once daily
- Maintenance of healed erosive esophagitis or relief of heartburn associated with non-erosive GERD
- No dose adjustment necessary
- H. pylori treatment
- CrCL ≥ 30 ml/min: 20 mg twice daily
- CrCL < 30 ml/min: not recommended
- Liver disease
- Healing of erosive esophagitis
- Child-Pugh A: 20 mg once daily
- Child-Pugh B and C: 10 mg once daily
- Maintenance of healed erosive esophagitis or relief of heartburn associated with non-erosive GERD
- No dose adjustment necessary
- H. pylori treatment
- Child-Pugh A: 20 mg twice daily
- Child-Pugh B and C: not recommended
- Side effects
- In trials, vonoprazan side effects, including gastritis (6%), abdominal pain (4%), and dyspepsia (4%), were uncommon and similar to lansoprazole [8]
- Contraindications / Precautions
- Gastric malignancy - response to vonoprazan does not preclude the presence of malignancy. Consider further workup in patients who have an incomplete response to therapy, early symptom recurrence, and the elderly.
- Acute tubulointerstitial nephritis - cases of acute tubulointerstitial nephritis (TIN) have been reported in patients receiving vonoprazan. Discontinue vonoprazan if TIN is suspected.
- Clostridioides difficile-associated diarrhea (CDAD) - observational studies have shown an association between PPIs and CDAD, especially in hospitalized patients. Consider CDAD in vonoprazan-treated patients who develop diarrhea and treat appropriately.
- Bone fracture - long-term PPI use has been associated with osteoporosis and bone fractures. Use caution in susceptible patients.
- Serious skin reactions - serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in patients receiving vonoprazan. Discontinue vonoprazan if a reaction is suspected.
- Vitamin B12 deficiency - vitamin B12 deficiency has been reported with long-term use of acid-suppressing drugs. Check B12 levels if signs of deficiency occur (e.g., macrocytic anemia, paresthesias, oral inflammation).
- Hypomagnesemia and mineral metabolism - long-term use of acid-suppressing drugs, including vonoprazan, has been associated with hypomagnesemia, which may cause or worsen hypokalemia and/or hypocalcemia. Patients receiving concomitant diuretics may be at greater risk. Consider checking magnesium and calcium levels before therapy and periodically thereafter. Use caution in patients receiving digoxin because hypomagnesemia can increase the risk of digoxin toxicity (e.g., heart block, arrhythmias).
- Interactions with diagnostic investigations for neuroendocrine tumors - serum chromogranin A (CgA), a biomarker used to diagnose neuroendocrine tumors, is elevated by acid-reducing drugs. CgA testing in patients receiving vonoprazan can cause false-positive results. Stop vonoprazan at least 14 days before checking serum CgA levels, and consider repeating the test if results are elevated.
- Secretin stimulation tests - secretin stimulation tests, which are used to diagnose gastrinomas, may be falsely hyper-responsive in patients receiving acid-reducing drugs. Vonoprazan should be held for at least 14 days before performing a test.
- Fundic gland polyps - fundic gland polyps have been reported in patients receing vonoprazan, especially with long-term use (> 1 year). Most polyps were asymptomatic and discovered incidentally on endoscopy.
- Kidney disease - see dosing
- Liver disease - see dosing
- Drug interactions
- NOTE: The drug interactions presented here are NOT all-inclusive. Other interactions may exist. Drug interaction checkers provide the most efficient and practical way to check for interactions among multiple medications. A free interaction checker is available from Drugs.com (see Drugs.com interactions checker).
- Clopidogrel - vonoprazan inhibits CYP2C19, which can prevent the conversion of clopidogrel to its active metabolite and reduce its antiplatelet activity. Consider another antiplatelet agent in patients receiving vonoprazan.
- Antiretrovirals - vonoprazan's acid-reducing effects may alter the absorption of antiretrovirals. Do not use vonoprazan with rilpivirine-containing products, atazanavir, and nelfinavir. For other antiretrovirals, consult the drug's prescribing information for recommendations on use with acid-reducing agents.
- Drugs affected by gastric pH - vonoprazan may alter the exposure of drugs whose absorption is affected by gastric pH (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole, itraconazole). Consult the drug's prescribing information for recommendations on use with acid-reducing agents.
- CYP3A4 inducers and substrates - vonoprazan is a CYP3A4 sensitive substrate and weak inhibitor. Strong and moderate CYP3A4 inducers reduce vonoprazan exposure, and coadministration is not recommended. CYP3A4 substrate exposure may be increased by vonoprazan; use caution with drugs that have a narrow therapeutic index.
- CYP2C19 substrates - vonoprazan is a CYP2C19 inhibitor and may increase CYP2C19 substrate exposure (e.g., citalopram, cilostazol). Use caution when combining and monitor for toxicity.
- Efficacy
- Healing of erosive esophagitis and relief of heartburn - a study (N=1024) comparing vonoprazan 20 mg daily to lansoprazole 30 mg in patients with erosive esophagitis found that vonoprazan was superior for endoscopic healing at 8 weeks (92.9% vs 84.6%, p<0.0001). Maintenance of healing at 24 weeks also favored vonoprazan (79.2% vs 72%), but heartburn-free days did not differ significantly between groups. [PMID 36228734]
- Non-erosive GERD - a study (N=772) comparing vonoprazan 10 or 20 mg daily to placebo in patients with non-erosive GERD found that both doses of vonoprazan were superior to placebo for heartburn-free days over 4 weeks (20 mg - 44.4%, 10 mg - 44.8%, placebo - 27.7%) [PMID 38750866]
- AGA 2024 recommendations for use [PMID 39269391]
- GERD
- Based on nonclinical factors (including cost, greater obstacles to obtaining medication, and fewer long-term safety data), clinicians should generally not use P-CABs as initial therapy for acid-related conditions in which clinical superiority has not been shown.
- Based on current costs in the United States, even modest clinical superiority of P-CABs over double-dose proton pump inhibitors (PPIs) may not make P-CABs cost-effective as first-line therapy.
- Clinicians should generally not use P-CABs as first-line therapy for patients with uninvestigated heartburn symptoms or nonerosive reflux disease. Clinicians may use P-CABs in selected patients with documented acid-related reflux who fail therapy with twice-daily PPIs.
- Although there is currently insufficient evidence for clinicians to use P-CABs as first-line on-demand therapy for patients with heartburn symptoms who have previously responded to antisecretory therapy, their rapid onset of acid inhibition raises the possibility of their utility in this population.
- Erosive esophagitis
- Clinicians should generally not use P-CABs as first-line therapy in patients with milder erosive esophagitis (EE) (Los Angeles classification of erosive esophagitis grade A/B EE). Clinicians may use P-CABs in selected patients with documented acid-related reflux who fail therapy with twice-daily PPIs.
- Clinicians may use P-CABs as a therapeutic option for the healing and maintenance of healing in patients with more severe EE (Los Angeles classification of erosive esophagitis grade C/D EE). However, given the markedly higher costs of the P-CAB presently available in the United States and the lack of randomized comparisons with double-dose PPIs, it is not clear that the benefits in endoscopic outcomes over standard-dose PPIs justify the routine use of P-CABs as first-line therapy.
- H. pylori
- Clinicians should use P-CABs in place of PPIs in eradication regimens for most patients with H pylori infection.
- Peptic ulcers
- Clinicians should generally not use P-CABs as first-line therapy in the treatment or prophylaxis of peptic ulcer disease.
- Although there is currently insufficient evidence for clinicians to use P-CABs as first-line therapy in patients with bleeding gastroduodenal ulcers and high-risk stigmata (e.g., active bleeding non-bleeding visible vessel, adherent clot), their rapid and potent acid inhibition raises the possibility of their utility in this population. [9]
PRICE ($) INFO
- $ = 0 - $50
- $$ = $51 - $100
- $$$ = $101 - $150
- $$$$ = > $150
- Pricing based on one month of therapy at standard dosing in an adult
- Pricing based on information from GoodRX.com®
- Pricing may vary by region and availability
BIBLIOGRAPHY
- 1 - PMID 34807007 - ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease, Am J Gastroenterol (2022)
- 2 - PMID 34807007 - Diagnosis and Management of Barrett’s Esophagus: An Updated ACG Guideline, Am J Gastroenterol (2022)
- 3 - PMID 35321279 - Barrett's esophagus: Review of natural history and comparative efficacy of endoscopic and surgical therapies, World J Gastrointest Oncol (2022)
- 4 - PMID 33351048 - Gastroesophageal Reflux Disease: A Review, JAMA (2020)
- 5 - PMID 23477993 - Gastro-oesophageal reflux disease, Lancet (2013)
- 6 - PMID 35183361 - AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review, Gastroenterology (2022)
- 7 - PMID 36341738 - Potassium-Competitive Acid Blocker Suppression of Gastric Acid in Erosive Esophagitis: Is Stronger and Longer Better?, Gastroenterology (2023)
- 8 - Voquezna prescribin ginformation
- 9 - PMID 39269391 - AGA Clinical Practice Update on Integrating Potassium-Competitive Acid Blockers Into Clinical Practice: Expert Review, Gastroenterology (2024)