VONOPRAZAN Drug Interactions: What You Need to Know

INTERACTIONS Table 9 and Table 10 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with VOQUEZNA and instructions for preventing or managing them. These recommendations are based on either drug interaction trials or predicted interactions due to the expected magnitude of interaction and potential for serious adverse reactions or loss of efficacy [see Clinical Pharmacology (12.3) ] . Consult the labeling of concomitantly used drugs to obtain further information about interactions with vonoprazan.

Table

9: Drug Interactions Affecting Drugs Co-Administered with VOQUEZNA and Interactions with Diagnostics Drugs Dependent on Gastric pH for Absorption Antiretrovirals Clinical Effect Vonoprazan reduces intragastric acidity [see Clinical Pharmacology (12.2) ], which may alter the absorption of antiretroviral drugs, leading to changes in the safety and/or effectiveness. Prevention or Management Rilpivirine-containing products Concomitant use with VOQUEZNA is contraindicated .

Atazanavir

Avoid concomitant use with VOQUEZNA.

Nelfinavir

Other antiretrovirals See the prescribing information of other antiretroviral drugs dependent on gastric pH for absorption prior to concomitant use with VOQUEZNA.

Other

Drugs (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole)

Clinical Effect

Vonoprazan reduces intragastric acidity [see Clinical Pharmacology (12.2) ] , which may decrease the absorption of drugs reducing their effectiveness. Prevention or Management See the prescribing information for other drugs dependent on gastric pH for absorption.

Combination

Therapy with Clarithromycin and/or Amoxicillin Clinical Effect Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and is contraindicated. Amoxicillin also has drug interactions. Prevention or Management See Contraindications and Warnings and Precautions in the prescribing information for clarithromycin.

See Drug

Interactions in the prescribing information for amoxicillin. Certain CYP3A Substrates Where Minimal Concentration Changes May Lead to Serious Toxicities Clinical Effect Vonoprazan is a weak CYP3A inhibitor [see Clinical Pharmacology (12.3) ] . Vonoprazan may increase exposure of CYP3A4 substrates, which may increase the risk of adverse reactions related to these substrates. Prevention or Management Frequently monitor concentrations and/or adverse reactions related to the substrate drugs when used with VOQUEZNA. Dosage reduction of substrate drugs may be needed. See prescribing information for the relevant substrate drugs. CYP2C19 Substrates (e.g., clopidogrel, citalopram, cilostazol)

Clinical Effect

Vonoprazan is a CYP2C19 inhibitor [see Clinical Pharmacology (12.3) ] . Vonoprazan may reduce plasma concentrations of the active metabolite of clopidogrel and may cause reduction in platelet inhibition. Vonoprazan may increase exposure of CYP2C19 substrate drugs (e.g., citalopram, cilostazol). Prevention or Management Clopidogrel Carefully monitor the efficacy of clopidogrel and consider alternative anti-platelet therapy. Citalopram and Cilostazol Carefully monitor patients for adverse reactions associated with citalopram and cilostazol. See the prescribing information for dosage adjustments.

Chromogranin

Test for Neuroendocrine Tumors Clinical Effect Vonoprazan reduces intragastric acidity [see Clinical Pharmacology (12.2) ] , which increases CgA levels and may cause false positive results in diagnostic investigations for neuroendocrine tumors . Prevention or Management Assess CgA levels at least 4 weeks after stopping VOQUEZNA treatment and repeat the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), use the same commercial laboratory for testing, as reference ranges between tests may vary. Interaction with Secretin Stimulation Test Clinical Effect Hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma. Prevention or Management Temporarily stop VOQUEZNA at least 4 weeks before assessing to allow gastrin levels to return to normal [see Clinical Pharmacology (12.2) ] .

Table

10: Drug Interactions Affecting VOQUEZNA When Co-Administered with Other Drugs Strong or Moderate CYP3A4 Inducers Clinical Effect Vonoprazan is a CYP3A substrate. Strong or moderate CYP3A inducers decrease vonoprazan exposure [see Clinical Pharmacology (12.3) ], which may reduce the effectiveness of VOQUEZNA. Prevention or Management Avoid concomitant use with VOQUEZNA. See full prescribing information for a list of clinically important drug interactions. ( 7 )

VOQUEZNA is contraindicated in patients with a known hypersensitivity to vonoprazan or any component of VOQUEZNA. Reactions have included anaphylactic shock [see Adverse Reactions (6.2) and Description (11) ] . VOQUEZNA is contraindicated with rilpivirine-containing products [see Drug Interactions (7) ] . For information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with VOQUEZNA, refer to the Contraindications section of the corresponding prescribing information. Known hypersensitivity to vonoprazan or any component of VOQUEZNA. ( 4 ) Rilpivirine-containing products. ( 4 , 7 )

AND PRECAUTIONS Gastric Malignancy : Symptomatic response to treatment does not preclude the presence of gastric malignancy; consider additional follow-up and diagnostic testing. ( 5.1 )

Acute Tubulointerstitial

Nephritis : Discontinue treatment and evaluate patients. ( 5.2 ) Clostridioides difficile -Associated Diarrhea (CDAD) : May be associated with an increased risk; use the shortest duration of treatment appropriate to the condition. ( 5.3 )

Bone

Fracture, including Osteoporosis-related Fracture : Use the shortest duration of treatment appropriate to the condition. ( 5.4 )

Severe Cutaneous Adverse

Reactions : Discontinue at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. ( 5.5 ) Vitamin B12 (Cobalamin) Deficiency : Long-term use may lead to malabsorption or deficiency; consider further workup if clinical symptoms are present. ( 5.6 ) Hypomagnesemia and Mineral Metabolism : Hypomagnesemia may lead to hypocalcemia and/or hypokalemia. Consider monitoring magnesium and calcium levels in at-risk patients, or if there is concomitant use of digoxin or other drugs that cause hypomagnesemia. ( 5.7 ) Interactions with Investigations for Neuroendocrine Tumors : Increased chromogranin A (CgA) levels may interfere with diagnostic investigations; temporarily stop VOQUEZNA at least 4 weeks before assessing CgA levels. ( 5.8 , 7 )

Fundic Gland

Polyps : Risk increases with long-term use; use the shortest duration of treatment appropriate to the condition. ( 5.9 )

5.1 Presence of Gastric Malignancy In adults, symptomatic response to therapy with VOQUEZNA 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 with VOQUEZNA. In older patients, also consider endoscopy.

5.2 Acute Tubulointerstitial Nephritis Acute tubulointerstitial nephritis (TIN) has been reported with VOQUEZNA <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . If suspected, discontinue VOQUEZNA and evaluate patients with suspected acute TIN.

5.3 Clostridioides difficile -Associated Diarrhea Published observational studies suggest that proton pump inhibitors (PPIs) may be associated with an increased risk of Clostridioides difficile -associated diarrhea (CDAD), especially in hospitalized patients. VOQUEZNA, another drug that blocks the proton pump to inhibit gastric acid production, may also increase the risk of CDAD. Consider CDAD in patients with diarrhea that does not improve <span class="opacity-50 text-xs">[see Adverse Reactions (6.2) ]</span> . Use the shortest duration of VOQUEZNA appropriate to the condition being treated. CDAD has been reported with use of nearly all antibacterial agents. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with VOQUEZNA, refer to the Warnings and Precautions section of the corresponding prescribing information.

5.4 Bone Fracture Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term therapy (a year or longer). Bone fracture, including osteoporosis-related fracture, has also been reported with vonoprazan. Use the shortest duration of VOQUEZNA appropriate to the condition being treated <span class="opacity-50 text-xs">[see Dosage and Administration (2.1) ]</span>. Patients at risk for osteoporosis-related fractures should be managed according to the established treatment guidelines .

5.5 Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with VOQUEZNA <span class="opacity-50 text-xs">[see Adverse Reactions (6.2) ]</span> . Discontinue VOQUEZNA at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.

5.6 Vitamin B12 (Cobalamin)

Deficiency

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 postmarketing with vonoprazan [see Adverse Reactions (6.2) ]. If clinical symptoms consistent with Vitamin B12 deficiency are observed in patients treated with VOQUEZNA consider further workup.

5.7 Hypomagnesemia and Mineral Metabolism Hypomagnesemia has been reported postmarketing with vonoprazan <span class="opacity-50 text-xs">[see Adverse Reactions (6.2) ]</span> . Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. Consider monitoring magnesium levels prior to initiation of VOQUEZNA and periodically in patients expected to be on prolonged treatment, in patients taking drugs that may have increased toxicity in the presence of hypomagnesemia (e.g., digoxin), or drugs that may cause hypomagnesemia (e.g., diuretics). Treatment of hypomagnesemia may require magnesium replacement and discontinuation of VOQUEZNA. Consider monitoring magnesium and calcium levels prior to initiation of VOQUEZNA and periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism). Supplement with magnesium and/or calcium, as necessary. If hypocalcemia is refractory to treatment, consider discontinuing VOQUEZNA.

5.8 Interactions with Diagnostic Investigations for Neuroendocrine Tumors Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Temporarily discontinue VOQUEZNA treatment at least 4 weeks before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary <span class="opacity-50 text-xs">[see Drug Interactions (7) and Clinical Pharmacology (12.2) ]</span> .

5.9 Fundic Gland Polyps Use of VOQUEZNA is associated with a risk of fundic gland polyps that increases with long-term use, especially beyond one year. Fundic gland polyps have been reported with vonoprazan in clinical trials and postmarketing use with PPIs. Most patients who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of VOQUEZNA appropriate to the condition being treated <span class="opacity-50 text-xs">[see Dosage and Administration (2.1) ]</span> .