Vonoprazan is a medication used in the treatment of gastrointestinal conditions such as erosive esophagitis and Helicobacter pylori bacterial infection. Erosive esophagitis is the erosion of the esophagus caused by inflammation of the mucous tissue lining the esophagus, caused by acid backup from the stomach. H. pylori bacterial infection attacks the lining of the stomach and duodenum and causes inflammation and ulcers. Vonoprazan blocks the mechanism that is responsible for acid secretion in the stomach.

Vonoprazan is a potassium-competitive acid blocker (PCAB), a type of proton pump inhibitor (PPI) that blocks the final step of acid production in the stomach. Vonoprazan accumulates in the acid-secreting parietal cells in the stomach wall and suppresses basal and stimulated acid secretion by competing with potassium to inhibit the hydrogen potassium (H/K) ATPase enzyme system. H/K ATPase is the proton pump that exchanges hydrogen for potassium and acidifies the stomach contents.

The mechanism of action of vonoprazan is different from other proton pump inhibitors, and unlike PPIs, PCABs do not require acid-resistant formulations and are not affected by genetic variations in CYP2C19, an enzyme that metabolizes these drugs. The FDA-approved uses of vonoprazan are:

• Healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults
• Maintain healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults
• Treatment of H. pylori infection in adults, in combination with amoxicillin and clarithromycin
• Treatment of H. pylori infection in adults, in combination with amoxicillin

• Do not use vonoprazan in patients with a known hypersensitivity to vonoprazan or any of its components.
• Do not use vonoprazan with rilpivirine-containing drugs.
• For information on contradictions when using antibacterial agents amoxicillin and clarithromycin, refer to the individual antibacterial agents.
• Symptomatic response to vonoprazan treatment does not preclude the presence of gastric cancer. Consider additional follow-up and testing in patients with suboptimal response or symptomatic relapse, and additionally, endoscopy in older patients.
• There have been reports of acute inflammation of the kidney’s tubules and surrounding tissues (tubulointerstitial nephritis) following treatment with vonoprazan. Discontinue vonoprazan and evaluate if the patient develops symptoms of kidney inflammation.
• Studies show treatment with proton pump inhibitors may be associated with an increased risk of Clostridioides difficile-associated diarrhea (CDAD). Vonoprazan also may increase the risk for CDAD, because this drug also inhibits proton pump and gastric acid production.
  • Use vonoprazan for the shortest period required for the condition being treated and evaluate for CDAD in patients with diarrhea that does not improve.
  • All antibacterial agents, including amoxicillin and clarithromycin which are used with vonoprazan, can cause CDAD. For more information specific to the antibacterial agents, refer to the prescribing information of the specific drug.
• PPI therapy, including vonoprazan, has been associated with bone loss and osteoporosis-related fractures of the hip, wrist or spine. The risk increases with high doses and prolonged treatment. Use vonoprazan for the shortest period required for the condition being treated, manage patients at risk for fractures according to established treatment guidelines.
• Some patients may experience severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis with vonoprazan treatment. Discontinue vonoprazan immediately in patients who develop such skin reactions or other hypersensitive reactions and treat appropriately.
• Prolonged use of acid blockers can lead to malabsorption of vitamin B12 (cobalamin). Evaluate patients who show signs and symptoms of vitamin B12 deficiency and treat appropriately.
• Vonoprazan can cause low magnesium levels (hypomagnesemia), which can further lead to low calcium (hypocalcemia) and/or low potassium (hypokalemia).
  • Consider monitoring magnesium levels before starting vonoprazan and periodically during treatment in patients expected to be on prolonged treatment, and in patients taking drugs that become more toxic in the presence of hypomagnesemia or drugs that can cause hypomagnesemia.
  • If the patient develops hypomagnesemia, treat with magnesium replacement therapy and discontinue vonoprazan, if required.
  • In addition to magnesium, also monitor calcium levels in patients at risk for hypocalcemia. Supplement magnesium and/or calcium as required.
• Vonoprazan may interfere with the results of diagnostic tests for neuroendocrine tumors.
• Vonoprazan therapy is associated with polyps in the secretory cells in the stomach (fundic gland polyps). The risk increases with long-term therapy. The polyps are mostly harmless, cause no symptoms and resolve with discontinuation of treatment. Use vonoprazan for the shortest period required for the condition being treated.

Common side effects of vonoprazan include:

Treatment of erosive esophagitis:

• Gastritis
• Diarrhea
• Abdominal distension
• Abdominal pain
• Nausea
• Indigestion (dyspepsia)
• High blood pressure (hypertension)
• Urinary tract infection
• COVID-19

Treatment of H. pylori infection:

• Diarrhea
• Abdominal pain
• Taste disorder (dysgeusia)
• Vulvovaginal Candida yeast infection (candidiasis)
• Headache
• Hypertension
• Nose and throat inflammation (nasopharyngitis)

Less common side effects of vonoprazan include:

Treatment of erosive esophagitis:

• Dry mouth
• Swallowing difficulty (dysphagia)
• Vomiting
• Gas (flatulence)
• Belching (eructation)
• Gastric and duodenal polyps
• Kidney inflammation (tubulointerstitial nephritis)
• Rapid heart rate (tachycardia)
• Swelling of extremities (peripheral edema)
• Weakness (asthenia)
• Upper respiratory infection
• Elevated liver function tests
• Diabetes mellitus
• Low red blood cell count (anemia)
• Excessive lymphocyte immune cells (lymphocytosis)
• Rash
• Hives (urticaria)
• Eczema
• Bone fracture
• Vertigo
• Dizziness
• Headache
• Fainting (syncope)
• Insomnia
• Depression

Treatment of H. pylori infection:

• Abdominal distension
• Constipation
• Dry mouth
• Oral inflammation (stomatitis)
• Tongue discomfort
• Nausea
• Vomiting
• Gastrointestinal polyps
• Gastric and/or duodenal ulcers
• Flatulence
• Indigestion (dyspepsia)
• Gastroesophageal reflux disease (GERD)
• Blood in stools (hematochezia)
• Overgrowth of kidney tissue (renal hypertrophy)
• Tubulointerstitial nephritis
• Vaginal discharge
• Rapid heart rate (tachycardia)
• Disturbance of heart rhythm (QT prolongation)
• Fatigue
• Fever (pyrexia)
• Decreased appetite
• Bone fracture
• Elevated liver function tests
• Viral infections
• Gastrointestinal viral or fungal infection
• Urinary tract infections
• Upper respiratory tract infection
• Pneumonia
• Cough
• Nasal polyps
• Mouth and throat (oropharyngeal) pain 
• Blood disorders including:
  • Anemia
  • High white blood cell count (leukocytosis)
  • Low white blood cell levels (leukopenia)
  • Low count of neutrophil immune cells (neutropenia)
• Dry skin
• Rash
• Dermatitis
• Drug hypersensitivity
• Anxiety
• Depression
• Insomnia
• Tension headache
• Dizziness
• Loss of taste (ageusia)
• Swelling around the eyes (orbital edema)

Other side effects of vonoprazan include:

• C. difficile overgrowth
• Jaundice
• Liver injury
• Liver failure
• Electrolyte disturbances including:
  • Low magnesium (hypomagnesemia)
  • Low potassium (hypokalemia)
  • Low calcium (hypocalcemia)
  • Vitamin B12 deficiency
• Low platelet count (thrombocytopenia)
• Drug eruption
• Erythema multiforme
• Stevens-Johnson syndrome
• Toxic epidermal necrosis
• Anaphylactic shock

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet

• 10 mg
• 20 mg

Adult:

Erosive Esophagitis

Treatment

• Indicated for healing of all grades of erosive esophagitis and relief of associated heartburn
• 20 mg orally once daily for 8 weeks

Maintenance

• Indicated to maintain healing of all grades of erosive esophagitis and relief of associated heartburn
• 10 mg orally once daily 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 twice daily plus amoxicillin 1,000 mg three times daily for 14 days
• Also available as copackaged product: Voquezna Dual Pak contains vonoprazan and amoxicillin

Triple therapy

• Vonoprazan 20 mg twice daily plus amoxicillin 1,000 mg three times daily plus clarithromycin 500 mg twice daily for 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/minute or above: No dosage adjustment required
  • eGFR below 30 mL/minute: Reduce dose to 10 mg orally once daily
• Maintenance of healed erosive esophagitis
  • All severities: No dosage adjustment required
• Treatment of H pylori infection
  • eGFR 30 mL/minute or above: No dosage adjustment required
  • eGFR below 30 mL/minute: 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 orally once daily
• 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

Pediatric:

• Safety and efficacy not established

Overdose

There is no information available on vonoprazan overdose.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of vonoprazan include:
  • rilpivirine
• Vonoprazan has serious interaction with at least 41 different drugs.
• Vonoprazan has moderate interaction with at least 42 different drugs.
• Vonoprazan has no listed mild interaction with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Available data on vonoprazan use in pregnant women are insufficient to determine a drug-associated risk of miscarriage, major birth defects, or other maternal or fetal adverse outcomes.
• In animal studies, vonoprazan administration during pregnancy caused fetal liver injury.
• It is not known if vonoprazan is present in breastmilk, or its effects on milk production or the breastfed infant. Vonoprazan and its metabolites are present in rat milk and are likely present in human breastmilk as well.
• Liver injury occurred in the offspring of mother rats that were administered vonoprazan. Do not breastfeed while on vonoprazan treatment, because of the risk for liver injury in the breastfeeding infant.

• Take vonoprazan exactly as prescribed.
• You may need periodic tests, especially if you are on long-term treatment with vonoprazan.
• Report immediately to your treating physician if you:
  • Develop any kidney-related symptoms
  • Develop diarrhea that does not improve
  • Experience any bone fractures, particularly in the wrist, spine or hip
  • Develop severe skin reactions or other allergic reactions
  • Symptoms of vitamin B12 deficiency such as muscle weakness, fatigue, nausea and increased heart rate
• Store vonoprazan safely out of reach of children.
• In case of overdose, seek medical attention or call Poison Control.