Dexilant

Proton Pump Inhibitors/PPIs

Dexlansoprazole systemic exposure (AUC) achieved from two 30 mg delayed-release orally disintegrating tablets is lower than the exposure obtained from a single 60 mg delayed-release capsule; formulations are not interchangeable.

Delayed-release capsules:
Administer without regard for food.
Swallow delayed-release capsules intact; do not chew or crush.
For patients with difficulty swallowing, the capsules may be opened and the contents sprinkled onto 1 tablespoonful of applesauce. Swallow immediately. Do not chew the granules. Do not prepare doses before the time of administration.
Oral syringe administration: Open capsules and empty contents into a clean container with 20 mL of water. Withdraw the entire mixture into an oral syringe. Gently swirl the oral syringe to prevent granules from settling. Administer the mixture immediately into the mouth; do not save for later use. Refill the oral syringe with 10 ml of water, swirl gently, and administer; repeat once more to flush oral syringe and administer full dose.
Nasogastric (NG) tube administration: Open capsules and empty content into a clean container with 20 mL of water. Withdraw the entire mixture into a catheter-tip syringe. Gently swirl the syringe to prevent granules from settling. Administer the mixture immediately through the nasogastric tube (16 French or greater) into the stomach; do not save for later use. Refill the syringe with 10 mL of water, swirl gently, and administer; repeat once more to flush the tube and administer full dose.
 
Delayed-release orally disintegrating tablets:
Administer at least 30 minutes before a meal.
Do not break or cut tablet. Do not chew microgranules.
Place tablet on tongue, allow it to disintegrate, and swallow microgranules without water. Alternatively, swallow tablet whole with water.
Instruct patients to avoid alcohol.
Oral syringe administration: Place one tablet in an oral syringe and draw up 20 mL of water. Gently swirl the oral syringe. After the tablet has dispersed, administer the mixture immediately into the mouth. Do not save for later use. Refill the oral syringe with 10 ml of water, swirl gently, and administer; repeat once more to flush oral syringe and administer full dose.
Nasogastric (NG) tube administration: Place one tablet in a catheter-tip syringe and draw up 20 mL of water. Gently shake the syringe to disperse. After the tablet has dispersed, swirl the syringe to keep microgranules from settling, and immediately administer the mixture through the nasogastric tube (8 French or greater) into the stomach. Do not save for later use. Refill the syringe with 10 mL of water, shake gently, and administer; repeat once more to flush the tube and administer full dose.

hematemesis / Delayed / 0-2.0
bezoar / Delayed / 0-2.0
seizures / Delayed / 0-2.0
thrombosis / Delayed / 0-2.0
bradycardia / Rapid / 0-2.0
myocardial infarction / Delayed / 0-2.0
pancreatitis / Delayed / Incidence not known
cholecystitis / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
anaphylactic shock / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
stroke / Early / Incidence not known
hearing loss / Delayed / Incidence not known
bone fractures / Delayed / Incidence not known
C. difficile-associated diarrhea / Delayed / Incidence not known
interstitial nephritis / Delayed / Incidence not known
renal failure / Delayed / Incidence not known

constipation / Delayed / 0-2.0
esophagitis / Delayed / 0-2.0
proctitis / Delayed / 0-2.0
gastritis / Delayed / 0-2.0
dysphagia / Delayed / 0-2.0
hemorrhoids / Delayed / 0-2.0
elevated hepatic enzymes / Delayed / 0-2.0
hepatomegaly / Delayed / 0-2.0
colic / Delayed / 0-2.0
cholelithiasis / Delayed / 0-2.0
hyperbilirubinemia / Delayed / 0-2.0
lymphadenopathy / Delayed / 0-2.0
thrombocytopenia / Delayed / 0-2.0
anemia / Delayed / 0-2.0
erythema / Early / 0-2.0
migraine / Early / 0-2.0
memory impairment / Delayed / 0-2.0
depression / Delayed / 0-2.0
colitis / Delayed / 0-2.0
dyspnea / Early / 0-2.0
palpitations / Early / 0-2.0
angina / Early / 0-2.0
chest pain (unspecified) / Early / 0-2.0
edema / Delayed / 0-2.0
sinus tachycardia / Rapid / 0-2.0
hypertension / Early / 0-2.0
hypokalemia / Delayed / 0-2.0
goiter / Delayed / 0-2.0
hypercalcemia / Delayed / 0-2.0
candidiasis / Delayed / 0-2.0
dyspareunia / Delayed / 0-2.0
ocular inflammation / Early / 0-2.0
jaundice / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
pernicious anemia / Delayed / Incidence not known
vitamin B12 deficiency / Delayed / Incidence not known
hallucinations / Early / Incidence not known
hypomagnesemia / Delayed / Incidence not known
hyperlipidemia / Delayed / Incidence not known
gout / Delayed / Incidence not known
diabetes mellitus / Delayed / Incidence not known
hypothyroidism / Delayed / Incidence not known
hyponatremia / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
dehydration / Delayed / Incidence not known
blurred vision / Early / Incidence not known
hypocalcemia / Delayed / Incidence not known
dysphonia / Delayed / Incidence not known
impotence (erectile dysfunction) / Delayed / Incidence not known
superinfection / Delayed / Incidence not known
pseudomembranous colitis / Delayed / Incidence not known
dysuria / Early / Incidence not known

diarrhea / Early / 4.8-4.8
nausea / Early / 2.9-2.9
eructation / Early / 0-2.0
dyspepsia / Early / 0-2.0
appetite stimulation / Delayed / 0-2.0
anorexia / Delayed / 0-2.0
halitosis / Early / 0-2.0
xerostomia / Early / 0-2.0
rash / Early / 0-2.0
pruritus / Rapid / 0-2.0
acne vulgaris / Delayed / 0-2.0
urticaria / Rapid / 0-2.0
libido decrease / Delayed / 0-2.0
paresthesias / Delayed / 0-2.0
insomnia / Early / 0-2.0
libido increase / Delayed / 0-2.0
tremor / Early / 0-2.0
anxiety / Delayed / 0-2.0
dizziness / Early / 0-2.0
dysgeusia / Early / 0-2.0
cough / Delayed / 0-2.0
pharyngitis / Delayed / 0-2.0
sinusitis / Delayed / 0-2.0
influenza / Delayed / 0-2.0
hyperventilation / Early / 0-2.0
hiccups / Early / 0-2.0
flushing / Rapid / 0-2.0
myalgia / Early / 0-2.0
musculoskeletal pain / Early / 0-2.0
arthralgia / Delayed / 0-2.0
asthenia / Delayed / 0-2.0
muscle cramps / Delayed / 0-2.0
weight gain / Delayed / 0-2.0
chills / Rapid / 0-2.0
dysmenorrhea / Delayed / 0-2.0
fever / Early / 0-2.0
menorrhagia / Delayed / 0-2.0
menstrual irregularity / Delayed / 0-2.0
ocular irritation / Rapid / 0-2.0
otalgia / Early / 0-2.0
tinnitus / Delayed / 0-2.0
vertigo / Early / 0-2.0
infection / Delayed / 1.9-1.9
vomiting / Early / 1.6-1.6
flatulence / Early / 1.6-1.6
abdominal pain / Early / 4.0
headache / Early / 2.0
tenesmus / Delayed / Incidence not known
gastric polyps / Delayed / Incidence not known
folliculitis / Delayed / Incidence not known
restless legs syndrome (RLS) / Delayed / Incidence not known
epistaxis / Delayed / Incidence not known
urinary urgency / Early / Incidence not known

Dexilant, Kapidex

Rx

Proton-pump inhibitor (PPI); R-enantiomer of lansoprazole
Used for healing and maintenance of erosive esophagitis and treatment of GERD
Available as a delay-release capsule and disintegrating tablet

30 mg PO once daily for 4 to 8 weeks. May increase the dose to 60 mg PO once daily in persons with partial response to the lower dose. Continue maintenance therapy at the lowest effective dose, including on demand or intermittent therapy, in persons who continue to have symptoms after discontinuation.

30 mg PO once daily for 4 weeks.

60 mg PO once daily for up to 8 weeks.

60 mg PO once daily for up to 8 weeks.

30 mg PO once daily. Periodically reassess need for continued PPI therapy. There is no clinical experience with prolonged, continuous treatment beyond 6 months.

30 mg PO once daily. Periodically reassess need for continued PPI therapy. There is no clinical experience with prolonged, continuous treatment beyond 16 weeks.

A dosage range of 30 to 60 mg PO once daily has been suggested; treat for up to 8 weeks and continue until the time of the follow-up endoscopy and biopsy. The guidelines support the use of PPI therapy for EoE based on reports of reductions in histologic features of disease from 42% in observational studies.

†Indicates off-label use

No dosage adjustments are recommended for patients with mild hepatic impairment (Child-Pugh Class A); however the maximum recommended dose for patients with moderate hepatic impairment (Child-Pugh Class B) is 30 mg PO daily. Avoid use in patients with severe impairment (Child-Pugh Class C) as no studies have been conducted.

Specific guidelines for dosage adjustment are not available; it appears that no dosage adjustment is necessary.
 
Intermittent hemodialysis Dexlansoprazole is not expected to be removed by hemodialysis.

Acalabrutinib: (Major) Avoid the concomitant use of acalabrutinib capsules and proton pump inhibitors (PPI), such as dexlansoprazole; decreased acalabrutinib exposure may occur resulting in decreased acalabrutinib effectiveness. Consider using the acalabrutinib tablet formlation or use an antacid or H2-blocker if acid suppression therapy is needed. Separate the administration of acalabrutinib capsules and antacids by at least 2 hours; give acalabrutinib capsules 2 hours before a H2-blocker. Acalabrutinib capsule solubility decreases with increasing pH values. The AUC of acalabrutinib was decreased by 43% when acalabrutinib capsules were coadministered with another PPI for 5 days.
Adagrasib: (Moderate) The plasma concentrations of dexlansoprazole may be elevated when administered concurrently with adagrasib. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Dexlansoprazole is a CYP3A substrate; adagrasib is a strong CYP3A inhibitor.
Albuterol; Budesonide: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Alendronate: (Moderate) Proton pump inhibitors (PPIs) are widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use proton pump inhibitors in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. It is not yet clear if all bisphosphonates would exhibit a loss of efficacy when PPIs are coadministered, but the results suggest that the interaction may occur across the class.
Alendronate; Cholecalciferol: (Moderate) Proton pump inhibitors (PPIs) are widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use proton pump inhibitors in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. It is not yet clear if all bisphosphonates would exhibit a loss of efficacy when PPIs are coadministered, but the results suggest that the interaction may occur across the class.
Amphetamine: (Moderate) Use amphetamine; dextroamphetamine and proton pump inhibitors concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
Amphetamine; Dextroamphetamine Salts: (Moderate) Use amphetamine; dextroamphetamine and proton pump inhibitors concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
Amphetamine; Dextroamphetamine: (Moderate) Use amphetamine; dextroamphetamine and proton pump inhibitors concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
Ampicillin: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.
Ampicillin; Sulbactam: (Major) Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.
Apalutamide: (Major) Avoid coadministration of dexlansoprazole with apalutamide due to decreased plasma concentrations of dexlansoprazole. Dexlansoprazole is a CYP3A4 and CYP2C19 substrate. Apalutamide is a strong CYP3A4 and CYP2C19 inducer.
Atazanavir: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%.
Atazanavir; Cobicistat: (Contraindicated) Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%. (Minor) The plasma concentrations of dexlansoprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while dexlansoprazole is a CYP3A4 substrate.
Belumosudil: (Major) Increase the dosage of belumosudil to 200 mg PO twice daily when coadministered with a proton pump inhibitor (PPI). Concomitant use may result in decreased belumosudil exposure and reduced belumosudil efficacy. Coadministration with other PPIs has decreased belumosudil exposure by 47% to 80% in healthy subjects.
Bisacodyl: (Minor) The concomitant use of bisacodyl oral tablets with drugs that raise gastric pH like proton pump inhibitors can cause the enteric coating of the bisacodyl tablets to dissolve prematurely, leading to possible gastric irritation or dyspepsia. When taking bisacodyl tablets, it is advisable to avoid PPIs within 1 hour before or after the bisacodyl dosage.
Bosutinib: (Major) Bosutinib displays pH-dependent aqueous solubility; therefore, concomitant use of bosutinib and proton-pump inhibitors, such as dexlansoprazole, may result in decreased plasma exposure of bosutinib. Consider using a short-acting antacid or H2 blocker if acid suppression therapy is needed; separate the administration of bosutinib and antacids or H2-blockers by more than 2 hours.
Budesonide: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Budesonide; Formoterol: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Budesonide; Glycopyrrolate; Formoterol: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Bumetanide: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Cabotegravir; Rilpivirine: (Contraindicated) Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine.
Capecitabine: (Moderate) Use caution if treatment with a proton pump inhibitor (PPI) is necessary in patients taking capecitabine, as progression-free survival (PFS) and overall survival (OS) may be adversely affected. The mechanism of this potential interaction is unknown and data are conflicting. In a posthoc, retrospective, subgroup analysis of a phase 3 clinical trial in patients with advanced or metastatic gastroesophageal cancer, administration of a PPI was associated with a significant decrease in PFS and OS in patients treated with capecitabine plus oxaliplatin (CapeOx) vs. patients who did not receive a PPI; a significant difference was not observed in the CapeOx plus lapatinib arm. Demographically, there were significantly more Asian patients in the PPI arm of this analysis; according to the manufacturer of capecitabine, Japanese patients have a 36% lower Cmax and 24% lower AUC for capecitabine compared with Caucasian patients. Additionally, there was not a significant increase in concentration dependent toxicities (e.g., hand-foot syndrome, rash, and diarrhea) or dose reductions in either arm. These observations are in line with a previous retrospective study in which patients with colorectal cancer receiving PPI treatment and adjuvant capecitabine also experienced poorer relapse-free survival compared with patients not receiving a PPI. Coadministration with antacids increased exposure to capecitabine and its metabolites, but this was not clinically significant or clinically relevant. Pharmacokinetic data on the impact of a PPI on capecitabine exposure are not available.
Carbamazepine: (Moderate) Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Carbamazepine induces hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If carbamazepine and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
Cefpodoxime: (Moderate) Cefpodoxime proxetil requires a low gastric pH for dissolution; therefore, concurrent administration with medications that increase gastric pH, such as proton pump inhibitors (PPIs) may decrease the bioavailability of cefpodoxime. When cefpodoxime was administered with high doses of antacids and H2-blockers, peak plasma concentrations were reduced by 24% and 42% and the extent of absorption was reduced by 27% and 32%, respectively. The rate of absorption is not affected.
Cefuroxime: (Major) Avoid the concomitant use of proton pump inhibitors (PPIs) and cefuroxime. Drugs that reduce gastric acidity, such as PPIs, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
Ceritinib: (Moderate) Monitor for dexlansoprazole-related adverse reactions (e.g., GI effects) if coadministration with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor, while dexlansoprazole is a CYP3A4 substrate. Plasma concentrations of dexlansoprazole may be elevated when administered concurrently with ceritinib.
Cobicistat: (Minor) The plasma concentrations of dexlansoprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while dexlansoprazole is a CYP3A4 substrate.
Cysteamine: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with proton pump inhibitors (PPIs). Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. Concomitant administration of omeprazole 20 mg did not alter the pharmacokinetics of delayed-release cysteamine when administered with orange juice; however, the effect of omeprazole on the pharmacokinetics of delayed-release cysteamine when administered with water have not been studied.
Dacomitinib: (Major) Avoid coadministration of dexlansoprazole with dacomitinib due to decreased plasma concentrations of dacomitinib which may impact efficacy. Coadministration with another proton pump inhibitor decreased the dacomitinib Cmax and AUC by 51% and 39%, respectively.
Darunavir; Cobicistat: (Minor) The plasma concentrations of dexlansoprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while dexlansoprazole is a CYP3A4 substrate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Minor) The plasma concentrations of dexlansoprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while dexlansoprazole is a CYP3A4 substrate.
Dasatinib: (Major) Do not administer proton pump inhibitors with dasatinib due to the potential for decreased dasatinib exposure and reduced efficacy. Consider using an antacid if acid suppression therapy is needed. Administer the antacid at least 2 hours prior to or 2 hours after the dose of dasatinib. Concurrent use of an proton pump inhibitor reduced the mean Cmax and AUC of dasatinib by 42% and 43%, respectively.
Delavirdine: (Major) Because proton pump inhibitors (PPIs) increase gastric pH, decreased delavirdine absorption may occur. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of PPIs with delavirdine is not recommended.
Dextroamphetamine: (Moderate) Use amphetamine; dextroamphetamine and proton pump inhibitors concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
Digoxin: (Moderate) Dexlansoprazole or other proton pump inhibitors (PPIs) can affect digoxin absorption due to their long-lasting effect on gastric acid secretion. Additionally, PPIs may slightly increase digoxin bioavailability. Patients with digoxin serum levels at the upper end of the therapeutic range may need to be monitored for potential increases in serum digoxin levels when a PPI is coadministered with digoxin. Finally, PPIs have been associated with hypomagnesemia. Becuase, low serum magnesium may lead to irregular heartbeat and increase the likelihood of serious cardiac arrhythmias, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and digoxin concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Dolutegravir; Rilpivirine: (Contraindicated) Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Minor) The plasma concentrations of dexlansoprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while dexlansoprazole is a CYP3A4 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) The plasma concentrations of dexlansoprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while dexlansoprazole is a CYP3A4 substrate.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Contraindicated) Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine.
Enzalutamide: (Major) Avoid coadministration of dexlansoprazole with enzalutamide due to decreased plasma concentrations of dexlansoprazole. Dexlansoprazole is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer.
Erlotinib: (Major) Avoid coadministration of erlotinib with dexlansoprazole if possible due to decreases in erlotinib plasma concentrations. Erlotinib solubility is pH dependent and solubility decreases as pH increases. Coadministration of erlotinib with medications that increase the pH of the upper gastrointestinal tract may decrease the absorption of erlotinib. Separation of doses may not eliminate the interaction since proton pump inhibitors affect the pH of the upper GI tract for an extended period of time. Increasing the dose of erlotinib is also not likely to compensate for the loss of exposure. Coadministration with another proton pump inhibitor decreased erlotinib exposure by 46% and the erlotinib Cmax by 61%.
Ethacrynic Acid: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Ethanol: (Major) Avoid alcohol-containing beverages when taking dexlansoprazole delayed-release orally disintegrating tablets (SoluTabs). Alcohol may modify the release rate of dexlansoprazole from the SoluTab, possibly resulting in reduced efficacy or worsening side effects.
Fluvoxamine: (Moderate) Fluvoxamine is a major inhibitor of the cytochrome P450 enzyme (CYP) 2C19. Several proton pump inhibitors (PPIs), including dexlansoprazole, are primary substrates of the CYP2C19 enzyme. Reduced metabolism and resulting elevated plasma concentrations of these PPIs may occur if combined with fluvoxamine. A single-dose pharmacokinetic study has shown that the mean AUC of omeprazole 40 mg was increased 2- to 6-fold when given after fluvoxamine 50 mg/day for 6 days. Monitor patients for PPI toxicity, such as headache or GI distress if these drugs are combined.
Food: (Moderate) Dexlansoprazole can be taken without regard to food. However, when taken with food, a slight decrease was observed in the percentage of time the intragastric pH exceeded 4 over a 24-hour dosing interval (57% after meal vs. 64% fasting).
Furosemide: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Gefitinib: (Major) Avoid coadministration of dexlansoprazole with gefitinib if possible due to decreased exposure to gefitinib, which may lead to reduced efficacy. If concomitant use is unavoidable, take gefitinib 12 hours after the last dose or 12 hours before the next dose of dexlansoprazole. Gefitinib exposure is affected by gastric pH. Coadministration with another drug to maintain gastric pH above 5 decreased gefitinib exposure by 47%.
Hydantoins: (Moderate) Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Fosphenytoin induces hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If fosphenytoin and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
Infigratinib: (Major) Avoid coadministration of infigratinib and gastric acid-reducing agents, such as proton pump inhibitors (PPIs). Coadministration may decrease infigratinib exposure resulting in decreased efficacy. If necessary, infigratinib may be administered two hours before or ten hours after an H2-receptor antagonist or two hours before or after a locally acting antacid. Coadministration with a PPI decreased infigratinib exposure by 45%.
Iron: (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of dexlansoprazole with rifampin due to the risk of decreased dexlansoprazole plasma concentrations which may decrease efficacy. Dexlansoprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of dexlansoprazole with rifampin due to the risk of decreased dexlansoprazole plasma concentrations which may decrease efficacy. Dexlansoprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
Itraconazole: (Moderate) When administering proton pump inhibitors with the 100 mg itraconazole capsule and 200 mg itraconazole tablet formulations, systemic exposure to itraconazole is decreased. Conversely, exposure to itraconazole is increased when proton pump inhibitors are administered with the 65 mg itraconazole capsule. Administer proton pump inhibitors at least 2 hours before or 2 hours after the 100 mg capsule or 200 mg tablet. Monitor for increased itraconazole-related adverse effects if proton pump inhibitors are administered with itraconazole 65 mg capsules.
Ketoconazole: (Major) Avoid use of proton pump inhibitors (PPIs) with ketoconazole. Medications that increase gastric pH may impair oral ketoconazole absorption.
Ledipasvir; Sofosbuvir: (Major) Solubility of ledipasvir decreases as gastric pH increases; thus, coadministration of ledipasvir; sofosbuvir with proton pump inhibitors (PPIs) may result in lower ledipasvir plasma concentrations. Ledipasvir can be administered with PPIs if given simultaneously under fasting conditions. The PPI dose should not exceed a dose that is comparable to omeprazole 20 mg/day.
Letermovir: (Moderate) Plasma concentrations of dexlansoprazole could be increased when administered concurrently with letermovir. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine. If these drugs are given together, monitor for dexlansoprazole-related adverse events. Dexlansoprazole is a CYP3A4 substrate. Letermovir is a moderate inhibitor of CYP3A4. When given with cyclosporine, the combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Levoketoconazole: (Major) Avoid use of proton pump inhibitors (PPIs) with ketoconazole. Medications that increase gastric pH may impair oral ketoconazole absorption.
Lonafarnib: (Moderate) The plasma concentrations of dexlansoprazole may be elevated when administered concurrently with lonafarnib. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Dexlansoprazole is a CYP3A4 substrate; lonafarnib is a strong CYP3A4 inhibitor.
Loop diuretics: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Lopinavir; Ritonavir: (Moderate) Concurrent administration of dexlansoprazole with ritonavir may result in elevated dexlansoprazole plasma concentrations. Dexlansoprazole is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and monitoring for adverse effects are advised if these drugs are administered together.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of dexlansoprazole by decreasing its systemic exposure. If used together, monitor for dexlansoprazole efficacy. Dexlansoprazole is a CYP3A4 and CYP2C19 substrate. Lumacaftor; ivacaftor is a strong inducer of CYP3A; in vitro data suggests lumacaftor may also induce CYP2C19.
Mefloquine: (Moderate) Proton pump inhibitors (PPIs) may increase plasma concentrations of mefloquine. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially patients with a neurological or psychiatric history.
Methotrexate: (Major) Avoid concomitant use of methotrexate and proton pump inhibitors (PPIs) due to the risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions; consider temporary withdrawal of the PPI in some patients receiving high-dose methotrexate. Concomitant use of methotrexate, primarily at high dose, and PPIs may increase and prolong serum concentrations of methotrexate, possibly leading to methotrexate toxicities.
Mitotane: (Moderate) Use caution if mitotane and dexlansoprazole are used concomitantly, and monitor for decreased efficacy of dexlansoprazole and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and dexlansoprazole is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of dexlansoprazole.
Mycophenolate: (Moderate) Concomitant administration of proton pump inhibitors (PPIs) with mycophenolate mofetil (Cellcept) appears to reduce MPA exposure AUC-12h (25.8 +/- 6.4 mg/L x h with omeprazole vs. 33.3 +/- 11.5 mg//L x h without omeprazole); however, the interaction does not appear to exist with mycophenolate sodium delayed-release tablets (Myfortic). Reduced systemic exposure of MPA after mycophenolate mofetil in the presence of a PPI appears to be due to impaired absorption of mycophenolate mofetil which may occur because of incomplete dissolution of mycophenolate mofetil in the stomach at elevated pH. The clinical significance of reduced MPA exposure is unknown; however patients should be evaluated periodically if mycophenolate mofetil is administered with a PPI. Of note, MPA concentrations appear to be reduced in the initial hours after mycophenolate mofetil receipt but increase later in the dosing interval because of enterohepatic recirculation. A second peak in the concentration-time profile of MPA is observed 612 hours after dosing due to enterohepatic recirculation. For example, the 12-hour plasma concentrations of MPA were similar among patients who received mycophenolate mofetil with or without omeprazole. The biphasic plasma concentration-time course of MPA due to extensive enterohepatic circulation hampers therapeutic drug monitoring of MPA. Drug exposure as measured by AUC-12h is the best estimator for the clinical effectiveness of mycophenolate, but measurement of full-dose interval MPA AUC-12h requires collection of multiple samples over a 12-hour period; MPA predose concentrations correlate poorly with MPA AUC-12h. The interaction does not appear to exist with Mycophenolate sodium (Myfortic).
Nelfinavir: (Major) Use of proton pump inhibitors with nelfinavir is not recommended. Coadministration may result in decreased nelfinavir exposure, subtherapeutic antiretroviral activity, and possibility resistant HIV mutations. In one study, concurrent use of nelfinavir with omeprazole resulted in decreased nelfinavir AUC, Cmax, and Cmin by 36%, 37%, and 39%, respectively.
Neratinib: (Major) Avoid concomitant use of neratinib with proton pump inhibitors due to decreased absorption and systemic exposure of neratinib; the solubility of neratinib decreases with increasing pH of the GI tract. Concomitant use with lansoprazole decreased neratinib exposure by 65%.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and proton pump inhibitors (PPIs), as PPIs may cause a reduction in nilotinib bioavailability. Nilotinib displays pH-dependent solubility with decreased solubility at a higher pH. PPIs inhibit gastric acid secretion and elevate the gastric pH. Administration of a single 400-mg nilotinib dose with multiple oral doses of esomeprazole 40 mg/day reduced the nilotinib AUC by 34% in a study in healthy subjects. Increasing the dose is unlikely to compensate for the loss of nilotinib exposure; additionally, separating the administration of these agents may not eliminate the interaction as PPIs affect the pH of the upper GI tract for an extended period of time.
Nirmatrelvir; Ritonavir: (Moderate) Concurrent administration of dexlansoprazole with ritonavir may result in elevated dexlansoprazole plasma concentrations. Dexlansoprazole is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and monitoring for adverse effects are advised if these drugs are administered together.
Octreotide: (Moderate) Coadministration of oral octreotide with proton pump inhibitors (PPIs) may require increased doses of octreotide. Coadministration of oral octreotide with drugs that alter the pH of the upper GI tract, including PPIs, may alter the absorption of octreotide and lead to a reduction in bioavailability. This interaction has been documented with esomeprazole and can occur with the other PPIs.
Pazopanib: (Major) Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours.
Phenobarbital: (Major) Avoid coadministration of dexlansoprazole with phenobarbital due to the risk of decreased dexlansoprazole plasma concentrations which may decrease efficacy. Dexlansoprazole is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of dexlansoprazole with phenobarbital due to the risk of decreased dexlansoprazole plasma concentrations which may decrease efficacy. Dexlansoprazole is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer.
Polyethylene Glycol; Electrolytes; Bisacodyl: (Minor) The concomitant use of bisacodyl oral tablets with drugs that raise gastric pH like proton pump inhibitors can cause the enteric coating of the bisacodyl tablets to dissolve prematurely, leading to possible gastric irritation or dyspepsia. When taking bisacodyl tablets, it is advisable to avoid PPIs within 1 hour before or after the bisacodyl dosage.
Posaconazole: (Major) The concurrent use of posaconazole immediate-release oral suspension and proton pump inhibitors (PPIs) should be avoided, if possible, due to the potential for decreased posaconazole efficacy. If used in combination, closely monitor for breakthrough fungal infections. PPIs increase gastric pH, resulting in decreased posaconazole absorption and lower posaconazole plasma concentrations. When a single 400 mg dose of posaconazole oral suspension was administered with esomeprazole (40 mg PO daily), the mean reductions in Cmax were 46% and the mean reductions in AUC were 32% for posaconazole. The pharmacokinetics of posaconazole delayed-release tablets and oral suspension are not significantly affected by PPIs. Additionally, posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of many PPIs (dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole). Coadministration may result in increased plasma concentration of the PPIs.
Primidone: (Major) Avoid coadministration of dexlansoprazole with primidone due to the risk of decreased dexlansoprazole plasma concentrations which may decrease efficacy. Dexlansoprazole is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer.
Ribociclib: (Minor) Use caution if coadministration of ribociclib with dexlansoprazole is necessary, as the systemic exposure of dexlansoprazole may be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor and dexlansoprazole is a CYP3A4 substrate.
Ribociclib; Letrozole: (Minor) Use caution if coadministration of ribociclib with dexlansoprazole is necessary, as the systemic exposure of dexlansoprazole may be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor and dexlansoprazole is a CYP3A4 substrate.
Rifampin: (Major) Avoid coadministration of dexlansoprazole with rifampin due to the risk of decreased dexlansoprazole plasma concentrations which may decrease efficacy. Dexlansoprazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
Rifapentine: (Major) Avoid coadministration of dexlansoprazole with rifapentine due to the risk of decreased dexlansoprazole plasma concentrations which may decrease efficacy. Dexlansoprazole is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Rilpivirine: (Contraindicated) Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine.
Risedronate: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
Ritonavir: (Moderate) Concurrent administration of dexlansoprazole with ritonavir may result in elevated dexlansoprazole plasma concentrations. Dexlansoprazole is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and monitoring for adverse effects are advised if these drugs are administered together.
Saquinavir: (Major) Coadministration with omeprazole results in significantly increased saquinavir concentrations. A similar interaction is expected with all proton pump inhibitors (PPIs). If saquinavir must be administered with PPIs, the patient should be closely monitored for saquinavir-related toxicities, including gastrointestinal symptoms, increased triglycerides, and deep vein thrombosis (DVT). Coadministration with omeprazole results in significantly increased saquinavir concentrations. In a small study, 18 healthy individuals received saquinavir 1000 mg (with ritonavir 100 mg) twice daily for 15 days; on days 11 through 15 omeprazole 40 mg was given once daily, which resulted in an 82% increase in the saquinavir AUC. A similar interaction is expected with all PPIs.
Secretin: (Major) Discontinue use of proton pump inhibitors before administering secretin. Patients who are receiving proton pump inhibitors at the time of stimulation testing may be hyperresponsive to secretin stimulation, falsely suggesting gastrinoma. The time required for serum gastrin concentrations to return to baseline after discontinuation of a proton pump inhibitor is specific to the individual drug.
Selpercatinib: (Major) Avoid coadministration of selpercatinib with dexlansoprazole due to the risk of decreased selpercatinib exposure which may reduce its efficacy. If concomitant use is unavoidable, selpercatinib must be taken with food. Coadministration under fasting conditions with another proton pump inhibitor decreased selpercatinib exposure by 69%; however, concomitant use increased selpercatinib exposure by 2% or less when it was administered with a meal.
Sofosbuvir; Velpatasvir: (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Solifenacin: (Moderate) The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
Sotorasib: (Major) Avoid coadministration of sotorasib and gastric acid-reducing agents, such as proton pump inhibitors (PPIs). Coadministration may decrease sotorasib exposure resulting in decreased efficacy. If necessary, sotorasib may be administered 4 hours before or 10 hours after a locally acting antacid. Coadministration with a PPI decreased sotorasib exposure by 57% under fed conditions and 42% under fasted conditions.
Sparsentan: (Major) Avoid concurrent use of sparsentan and proton pump inhibitors (PPIs) due to the risk for decreased sparsentan exposure which may reduce its efficacy. Medications that affect gastric pH may reduce sparsentan absorption.
St. John's Wort, Hypericum perforatum: (Major) Avoid concomitant use of St. John's wort with the proton pump inhibitors (PPIs) as PPI exposure may be decreased, reducing their efficacy. PPIs are CYP3A4 and CYP2C19 substrates and St. John's wort is a strong CYP3A4 and CYP2C19 inducer. For example, coadministration of omeprazole with St. John's wort decreased omeprazole plasma concentrations by approximately 40%.
Sucralfate: (Moderate) Sucralfate has been shown to delay the absorption and reduce the bioavailability of oral lansoprazole by about 17%. Dexlansoprazole should be taken no less than 30 minutes before sucralfate if these drugs are to be used concomitantly. Concurrent administration of oral dexlansoprazole and antacids may reduce the bioavailability of dexlansoprazole; except when the antacids are given at least 30 minutes to one hour before dexlansoprazole administration.
Tacrolimus: (Moderate) Monitor tacrolimus whole blood concentrations and adjust tacrolimus dose as needed to maintain therapeutic concentrations during concomitant use of dexlansoprazole. Coadministration may increase serum concentrations of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19.
Thiazide diuretics: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Thyroid hormones: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
Tipranavir: (Moderate) Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Tipranavir markedly induces the hepatic cytochrome P-450 enzyme CYP2C19, an enzyme responsible for the metabolism of PPIs. However, since tipranavir is not given unless it is co-prescribed with ritonavir, a known marked enzyme inhibitor, a reduction in PPI metabolism may be unlikely to occur. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If tipranavir and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
Tolterodine: (Moderate) The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
Torsemide: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Trospium: (Moderate) The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
Tucatinib: (Minor) The plasma concentrations of dexlansoprazole may be elevated when administered concurrently with tucatinib. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Dexlansoprazole is a CYP3A4 substrate; tucatinib is a strong CYP3A4 inhibitor.
Voriconazole: (Minor) Use caution if coadministration of voriconazole with dexlansoprazole is necessary, as the systemic exposure of dexlansoprazole may be increased resulting in increase in treatment-related adverse reactions. Voriconazole is a strong inhibitor of CYP3A4 and also inhibits CYP2C19. Dexlansoprazole is a substrate of CYP3A and CYP2C19.
Warfarin: (Moderate) Monitor the INR in patients receiving warfarin with proton pump inhibitors. Increases in INR may lead to abnormal bleeding. Adjust the warfarin dose to maintain the target INR.

Dexilant/Dexlansoprazole/Kapidex Oral Cap DR Pellets: 30mg, 60mg

60 mg/day PO for delayed-release capsules; 30 mg/day for delayed-release orally disintegrating tablets.

60 mg/day PO for delayed-release capsules; 30 mg/day for delayed-release orally disintegrating tablets.

60 mg/day PO for delayed-release capsules; 30 mg/day for delayed-release orally disintegrating tablets.

12 years: 60 mg/day PO for delayed-release capsules; 30 mg/day for delayed-release orally disintegrating tablets.
1 to 11 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Dexlansoprazole, a proton-pump inhibitor (PPI), suppresses gastric acid secretion by gastric parietal cells. It is the R-enantiomer of lansoprazole and represents > 80% of the circulating drug after oral administration of lansoprazole. Dexlansoprazole inhibits the H+/K+ ATPase enzyme required for gastric-acid pump activation, thereby irreversibly blocking the final step of acid output from the parietal cells. A significant increase in gastric pH and decrease in basal acid output follow oral administration. Dexlansoprazole capsules contain two types of granules, each of which dissolve at a different pH. This unique dual delayed release formulation allows for two distinct phases of drug release. The second phase of drug release purportedly inhibits proton pumps that were initially uninhibited or that were reactivated after the first phase of H+/K+ ATPase enzyme inhibition. Dexlansoprazole exerts an inhibitory effect on gastric acid for at least 24 hours, which allows a once-daily dosing schedule.
 
Similar to lansoprazole, hypergastrinemia can occur during dexlansoprazole therapy. Mean fasting gastrin concentrations increase from baseline during dexlansoprazole treatment. Patients treated for more than 6 months experienced a mean serum gastrin level increase during the first 3 months of treatment. Increases leveled off and were stable for the remainder of the 6-month treatment period. One month after treatment discontinuation, serum gastrin concentrations returned to pre-treatment levels. Although prolonged hypergastrinemia has been associated with gastric tumors, long-term studies of proton pump inhibitors have not revealed an increased development of tumors, which was an initial concern in animal models.

Dexlansoprazole is administered orally. Plasma protein binding of dexlansoprazole ranges from 96.1% to 98.8% in healthy subjects. It is not known whether dexlansoprazole is excreted in human milk; however, racemate lansoprazole is excreted into animal breast milk and possibly into human breast milk. Hepatic metabolism of dexlansoprazole is extensive. Oxidative metabolites are formed by the cytochrome P450 (CYP) enzyme system; hydroxylation occurs mainly by CYP2C19 and oxidation by CYP3A4. The plasma elimination half-life, which is approximately 1 to 2 hours in adults, is not related to the gastric antisecretory effect, which lasts more than 24 hours. No unchanged dexlansoprazole is excreted in the urine.
 
Affected cytochrome P450 (CYP450) enzymes and drug transporters: CYP2C19, CYP3A4
Dexlansoprazole is a substrate of the cytochrome P450 system via the CYP2C19 and CYP3A4 isoenzymes. Therefore, drug interactions with agents that may inhibit, induce, or otherwise competitively affect the metabolism of dexlansoprazole are possible.

Dexlansoprazole systemic exposure (AUC) achieved from two 30 mg delayed-release orally disintegrating tablets is lower than the exposure obtained from a single 60 mg delayed-release capsule; formulations are not interchangeable.
Delayed-release capsules: The capsules are formulated to have a dual delayed release mechanism that results in a plasma concentration-time profile with two distinct peaks; the first peak occurs 1 to 2 hours after administration, followed by a second peak within 4 to 5 hours. In clinical evaluation, administration of the 30 mg and 60 mg capsules to adult patients led to an approximately dose proportional increase in the mean Cmax (658 ng/mL vs. 1,397 ng/mL, respectively) and AUC (3,275 ng x hour/mL vs. 6,529 ng x hour/mL, respectively). Similar increases were noted in pediatric patients 12 to 17 years of age: Cmax (691 ng/mL vs. 1,136 ng/mL, respectively) and AUC (2,886 ng x hour/mL vs. 5,120 ng x hour/mL, respectively). The capsules can be taken without regard to food; however, when administered under various fed conditions, the Cmax and AUC were elevated (12% to 55% and 9% to 37%, respectively), and the effects on Tmax were variable (range, -0.7 to 3 hours). Mixing the capsule granules with water for administration via nasogastric tube or syringe does not alter bioavailability.
Delayed-release orally disintegrating tablets: Dexlansoprazole delayed-release orally disintegrating tablets (SoluTabs) should be administered at least 30 minutes before a meal. Under fasting conditions, the median Tmax is 4 hours (range, 1 to 6 hours), Cmax is 688 ng/mL, and the AUC is 2,866 ng x hour/mL. However, when administered with a high-fat meal (1,000 calories, 50% fat), drug absorption is delayed resulting in a prolonged median Tmax of 6 hours and decreased Cmax by an average of 38%; overall drug exposure (AUC) is not affected by food. Mixing the SoluTabs with water for administration via nasogastric tube or syringe does not alter bioavailability.

There are no adequate and well-controlled studies with dexlansoprazole use during pregnancy. However, dexlansoprazole is the R-enantiomer of lansoprazole, and published observational studies of lansoprazole use during human pregnancy did not demonstrate an association of adverse pregnancy-related outcomes. A reproduction study conducted in rabbits revealed no evidence of harm to the fetus at dexlansoprazole doses approximately 9-fold the maximum recommended human dose (60 mg) based on body surface area. A pre- and postnatal developmental toxicity study in rats during organogenesis through lactation at 1.8 times the maximum recommended human dexlansoprazole dose based on AUC produced reductions in the offspring in femur weight, femur length, crown-rump length and growth plate thickness (males only) on postnatal day 21; these effects were associated with reduction in body weight gain. In a prospective study, outcomes from pregnant women (n= 62) administered lansoprazole (30 mg/day median dose) were compared to a pregnant control group (n=868) who did not take any proton pump inhibitors (PPIs). There was no difference in the rate of major malformations between women exposed to PPIs and the control group, (RR = 1.04, 95% CI 0.25 to 4.21). In a retrospective cohort study covering all live births in Denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of first trimester exposure to lansoprazole in 794 live births. In a meta-analysis that compared 1,530 pregnant women exposed to PPIs in at least the first trimester with 133,410 unexposed pregnant women, there were no significant increases in risk with exposure to PPIs for major congenital malformations (OR =1.12, 95% CI 0.86 to 1.45) or for spontaneous abortions (OR = 1.29, 95% CI 0.84 to 1.97). Guidelines recommend a trial of lifestyle modifications as first-line therapy for heartburn and gastroesophageal reflux disease (GERD) during pregnancy, followed by antacids if lifestyle adjustments are ineffective. For ongoing symptoms, histamine type 2-receptor antagonists (H2RAs) can be used. Proton pump inhibitors should be reserved for pregnant patients who fail H2RA therapy.

It is not known whether dexlansoprazole, the R-enantiomer of lansoprazole, is excreted in human milk. However, lansoprazole and its metabolites are present in rat milk. The clinical effects of proton pump inhibitor (PPI) exposure on the breastfed infant or on milk production have not been confirmed and PPI use is not recommended while breast-feeding; consider the developmental and health benefits of breast-feeding along with the clinical need for dexlansoprazole and any potential adverse effects on the breastfed infant or from the underlying maternal condition. According to guidelines, if heartburn/gastroesophageal reflux (GERD) symptoms persist after delivery, antacids and sucralfate are safe to use because they are not concentrated in breast milk. Histamine type 2-receptor antagonists (H2RAs) are excreted in breast milk, but cimetidine and famotidine are considered safe for use during lactation and may be used if symptoms persist despite antacid use.