Vonoprazan

Gastroesophageal Reflux Disease (GERD)

Vonoprazan is primarily used to manage conditions related to acid reflux. These include:

• Erosive Esophagitis: It is used to treat and heal inflammation and sores in the lining of the esophagus caused by stomach acid.
• Maintenance of Healing: It is used to help prevent erosive esophagitis from returning once it has been treated.
• Heartburn Relief: It is used to treat the heartburn associated with non-erosive GERD in adults.

H. pylori Infection

Vonoprazan is also used to treat Helicobacter pylori (H. pylori) infection, a type of bacteria that can cause stomach ulcers. For this purpose, it is used as part of a combination treatment plan that includes antibiotics such as amoxicillin and clarithromycin.

Vonoprazan belongs to a class of medications called potassium-competitive acid blockers (PCABs). It works by reducing the production of acid in the stomach by targeting the proton pumps in the stomach lining.

These proton pumps represent the final step in the process of secreting stomach acid. Vonoprazan works by competing with potassium ions to bind to these pumps. When the medication binds to the pump, it prevents the pump from releasing acid into the stomach.

By lowering stomach acid levels, vonoprazan helps with several conditions:

• Healing: It allows the lining of the esophagus to heal if it has been damaged by acid reflux (erosive esophagitis).
• Symptom Relief: It reduces the frequency and severity of heartburn symptoms.
• Infection Treatment: When used with antibiotics, it creates a less acidic environment in the stomach, which helps the antibiotics work more effectively to eliminate H. pylori bacteria.

Unlike some older acid-reducing drugs, vonoprazan does not need to be activated by stomach acid to start working, which may allow it to suppress acid production more consistently.

Common Side Effects

• Stomach pain
• Diarrhea
• Constipation
• Nausea
• Gas
• Headache

Serious Side Effects

Contact your healthcare provider immediately if you experience any of the following:

• Severe diarrhea: Watery or bloody stools, stomach cramps, or fever, which may indicate a serious bacterial infection (Clostridioides difficile).
• Kidney problems: Signs of kidney inflammation, such as blood in the urine or changes in how much you urinate.
• Lupus-like symptoms: Joint pain or a skin rash on the cheeks or arms that worsens in sunlight.
• Low magnesium levels: Symptoms include seizures, dizziness, irregular heartbeat, or muscle spasms.
• Bone fractures: Long-term use may increase the risk of hip, wrist, or spine fractures.
• Vitamin B12 deficiency: Taking this medication for more than three years may lead to a deficiency.
• Stomach polyps: Long-term use may cause small growths called fundic gland polyps in the stomach lining.

Allergic Reactions

Serious allergic reactions, including anaphylaxis, have been reported with vonoprazan. Signs of a reaction may include rash, hives, swelling of the face or throat, and difficulty breathing. If these symptoms occur, medical attention is typically required immediately.

Kidney Problems

Acute tubulointerstitial nephritis, a type of kidney inflammation, can occur at any time during treatment with vonoprazan. This condition may lead to kidney failure. Healthcare providers may monitor kidney function, especially in patients with pre-existing kidney disease.

Severe Diarrhea

The use of acid-reducing medications like vonoprazan may increase the risk of Clostridioides difficile-associated diarrhea (CDAD). This is a severe form of diarrhea caused by a bacterial infection. Symptoms include watery stools, stomach pain, and fever that does not improve.

Bone Fractures

Long-term use or high doses of vonoprazan may increase the risk of fractures in the hip, wrist, or spine. This risk is most significant for individuals who take the medication for a year or longer. Using the lowest effective dose for the shortest duration possible is generally recommended.

Nutritional and Electrolyte Changes

• Magnesium Levels: Long-term use (typically over one year) can lead to low magnesium levels in the blood (hypomagnesemia). Symptoms may include tremors, muscle spasms, or an irregular heartbeat. In some cases, magnesium supplements or stopping the medication may be necessary.
• Vitamin B-12 Deficiency: Using acid-suppressing drugs for more than three years can interfere with the body's ability to absorb vitamin B-12, potentially leading to a deficiency.

Stomach Growths

Extended use of vonoprazan is associated with an increased risk of developing fundic gland polyps. These are small, non-cancerous growths on the lining of the stomach. The risk typically increases the longer the medication is used.

Drug Interactions

Because vonoprazan reduces stomach acid, it can change how the body absorbs other medications. This is particularly important for certain cancer treatments, antifungals, and medications used to treat HIV. Healthcare providers should review all current medications before starting vonoprazan.

Pregnancy

It is currently unknown if vonoprazan will cause harm to an unborn baby. If you are pregnant or planning to become pregnant, you should discuss the potential risks and benefits with your healthcare provider before using this medication. If you become pregnant while taking vonoprazan, contact your doctor immediately.

Breastfeeding

It is not known whether vonoprazan passes into human breast milk or how it might affect a nursing infant. Because the effects are unknown, it is important to talk to your doctor if you are breastfeeding or planning to breastfeed while taking this medication.

Available Forms

Vonoprazan is available in the following form for oral administration:

• Oral tablet

Vonoprazan is also supplied in co-packaged treatment kits. These kits contain vonoprazan tablets along with other medications, such as antibiotics, to be taken together as part of a specific treatment plan.

FDA Approval Status

Vonoprazan, marketed under the brand name Voquezna, is approved by the U.S. Food and Drug Administration (FDA) as a potassium-competitive acid blocker (PCAB). It is used to reduce stomach acid production for several specific gastrointestinal conditions.

Approved Indications

The FDA has approved vonoprazan for the following uses in adults:

• Erosive Esophagitis: For the healing of all grades of erosive esophagitis and the maintenance of healing to prevent recurrence.
• Heartburn Relief: For the treatment of heartburn associated with erosive esophagitis.
• H. pylori Infection: For the treatment of Helicobacter pylori infection when used in combination with amoxicillin and clarithromycin (triple therapy) or amoxicillin alone (dual therapy).

Regulatory History

The FDA first approved vonoprazan in May 2022 as part of co-packaged kits containing antibiotics for the treatment of H. pylori. In November 2023, the FDA expanded its approval to include vonoprazan as a standalone tablet for the healing and maintenance of erosive esophagitis and associated heartburn.

Safety and Regulatory Notifications

There are currently no boxed warnings or Risk Evaluation and Mitigation Strategies (REMS) associated with vonoprazan. While the FDA has issued safety communications regarding potential risks like low magnesium levels for long-term use of proton pump inhibitors (PPIs), vonoprazan belongs to a different class of acid-suppressing medications known as PCABs.

Initial FDA Approval

The U.S. Food and Drug Administration (FDA) first approved vonoprazan in May 2022. This initial approval was for its use in co-packaged combination therapies with antibiotics to treat Helicobacter pylori (H. pylori) infection in adults.

Approval for Erosive Esophagitis

In November 2023, the FDA expanded the approval of vonoprazan to include the treatment of erosive esophagitis, a condition where the esophagus is damaged by stomach acid. The approved uses for this condition include:

• Healing of all grades of erosive esophagitis.
• Maintenance of healing of erosive esophagitis.
• Relief of heartburn associated with erosive esophagitis.

Regulatory Significance

Vonoprazan is the first medication in a class known as potassium-competitive acid blockers (PCABs) to receive FDA approval. It provides an alternative to other acid-reducing medications, such as proton pump inhibitors, for managing acid-related gastrointestinal disorders.