Vonoprazan-Amoxicillin-Clarithromycin

Vonoprazan-Amoxicillin-Clarithromycin is a prescription medication indicated:

• for healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults
• to maintain healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults
• for the relief of heartburn associated with non-erosive gastroesophageal reflux disease (GERD) in adults
• in combination with amoxicillin and clarithromycin for the treatment of Helicobacter pylori (H. pylori) infection in adults
• in combination with amoxicillin for the treatment of H. pylori infection in adults

Donanemab is available under the following different brand names: Voquezna

Common side effects of Vonoprazan-Amoxicillin-Clarithromycin include:

• stomach inflammation 
• nausea 
• diarrhea 
• indigestion 
• stomach bloating 
• high blood pressure 
• stomach pain 
• urinary tract infection
• temporary changes in the sense of taste
• vaginal yeast infection
• headache
• cold-like symptoms

Serious side effects of Vonoprazan-Amoxicillin-Clarithromycin include:

• acute tubulointerstitial nephritis: symptoms include a decrease in urination or blood in urine
• diarrhea caused by an infection (Clostridioides difficile): symptoms include watery stools, stomach pain, or fever that do not go away
• bone fractures (hip, wrist, or spine)
• severe skin reactions: symptoms include blistering, peeling, or bleeding on any part of the skin (including lips, eyes, mouth, nose, genital, hands, or feet), fever, chills, body aches, shortness of breath, or enlarged lymph nodes
• low Vitamin B-12 levels: symptoms include irregular heartbeat, shortness of breath, lightheadedness, tingling or numbness in the arms and legs, muscle weakness, pale skin, feeling tired, or mood changes
• low magnesium levels in the body: symptoms include seizures, dizziness, irregular heartbeat, jitteriness, muscle aches or weakness, or spasms of hands, feet, or voice
• stomach growths (fundic gland polyps)

Rare side effects of Vonoprazan-Amoxicillin-Clarithromycin include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms include sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

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

Adult dosage

Tablet

• 10 mg
• 20 mg

Erosive Esophagitis

Adult dosage

• Treatment
  • 20 mg orally once daily x 8 weeks
• Maintenance
  • 10 mg orally once daily for up to 6 months

Helicobacter pylori infection

Adult dosage

• Dual therapy
  • Vonoprazan-Amoxicillin-Clarithromycin 20 mg twice daily plus amoxicillin 1,000 mg three times a day x 14 days
• Triple therapy
  • Vonoprazan-Amoxicillin-Clarithromycin 20 mg twice daily plus amoxicillin 1,000 mg three times a day plus clarithromycin 500 mg twice daily x 14 days

Heartburn

Adult dosage

• 10 mg orally once daily x 4 weeks

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Vonoprazan-Amoxicillin-Clarithromycin has severe interactions with the following drug:
  • rilpivirine
• Vonoprazan-Amoxicillin-Clarithromycin has serious interactions with at least 41 other drugs
• Vonoprazan-Amoxicillin-Clarithromycin has moderate interactions with at least 42 other drugs
• Vonoprazan-Amoxicillin-Clarithromycin has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Known hypersensitivity to Vonoprazan-Amoxicillin-Clarithromycin or any component of drug product
• Rilpivirine-containing products, owing to inhibition of gastric pH by Vonoprazan-Amoxicillin-Clarithromycin
• Contraindication involving the use of clarithromycin and amoxicillin 

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Vonoprazan-Amoxicillin-Clarithromycin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Vonoprazan-Amoxicillin-Clarithromycin?”

Cautions

• Acute tubulointerstitial nephritis reported; if suspected, discontinue the drug and evaluate the patient
• Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) reported; discontinue the 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 post-marketing with Vonoprazan-Amoxicillin-Clarithromycin; consider further workup if clinical symptoms consistent with vitamin B12 deficiency observed
• Presence of gastric malignancy
  • Symptomatic response to Vonoprazan-Amoxicillin-Clarithromycin does not preclude the 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 an increased risk of Clostridioides difficile-associated diarrhea (CDAD), especially in hospitalized patients
  • Vonoprazan-Amoxicillin-Clarithromycin, 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-Amoxicillin-Clarithromycin for the shortest duration that is appropriate
• Bone fracture
  • PPIs may increase the 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 (more than a year)
  • Bone fracture, including osteoporosis-related fracture, has also been reported with Vonoprazan-Amoxicillin-Clarithromycin
  • Use Vonoprazan-Amoxicillin-Clarithromycin for the shortest duration that is appropriate
  • Manage patients at risk for osteoporosis-related fractures according to established treatment guidelines
• Hypomagnesemia and mineral metabolism
  • Hypomagnesemia reported post-marketing
  • 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-Amoxicillin-Clarithromycin
  • 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-Amoxicillin-Clarithromycin
• Fundic gland polyps
  • Use associated with risk of fundic gland polyps that increases with long-term use, especially more than a year
  • Fundic gland polyps reported in clinical trials and post-marketing use with PPIs
  • Most patients who developed fundic gland polyps were asymptomatic and the polyps were identified incidentally on endoscopy
  • Use Vonoprazan-Amoxicillin-Clarithromycin for the 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-Amoxicillin-Clarithromycin 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-Amoxicillin-Clarithromycin 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-Amoxicillin-Clarithromycin may reduce plasma concentrations of clopidogrel’s active metabolite and may cause a reduction in platelet inhibition
    • Vonoprazan-Amoxicillin-Clarithromycin may increase the exposure of CYP2C19 substrate drugs (eg, citalopram, cilostazol)
  • Strong or moderate CYP3A4 inducers
    • Avoid coadministration
    • Strong or moderate CYP3A inducers decrease Vonoprazan-Amoxicillin-Clarithromycin 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-Amoxicillin-Clarithromycin at least 14 days before assessing CgA levels and consider repeating the 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-Amoxicillin-Clarithromycin at least 14 days before assessing to allow gastrin levels to return to baseline

Pregnancy and Lactation

• Available data from pharmacovigilance reports with Vonoprazan-Amoxicillin-Clarithromycin 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)
• Lactation
  • There are no data regarding the presence of Vonoprazan-Amoxicillin-Clarithromycin in human milk, the effects on the breastfed infant, or the effects on milk production
  • Vonoprazan-Amoxicillin-Clarithromycin and its metabolites are present in rat milk; liver injury occurred in offspring from pregnant and lactating rats administered oral Vonoprazan-Amoxicillin-Clarithromycin at AUC exposures approximately equal to and greater than the MRHD