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  • CLASSES

    Proton Pump Inhibitors/PPIs

    DEA CLASS

    Rx

    DESCRIPTION

    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

    COMMON BRAND NAMES

    Dexilant

    HOW SUPPLIED

    Dexilant Oral Cap DR Pellets: 30mg, 60mg

    DOSAGE & INDICATIONS

    For the symptomatic treatment of non-erosive gastroesophageal reflux disease (GERD), including treatment of pyrosis (heartburn) related to GERD.
    NOTE: Dexlansoprazole is not used for occasional heartburn.
    Oral dosage
    Adults

    30 mg PO once daily for 4 weeks. Per treatment guidelines, initiate empiric therapy based on a presumptive diagnosis of GERD in the setting of typical symptoms of heartburn and regurgitation. For patients with partial response to once daily therapy, consider dexlansoprazole 30 mg PO twice daily, or, consider a one-time switch to a different PPI. Refer non-responders for further evaluation. Consider maintenance therapy for patients who continue to have symptoms after PPI discontinuation; the lowest effective dose, including on demand or intermittent therapy should be used with regular assessment of the need for continued PPI therapy. Alternatively, step down maintenance therapy to an H2 blocker is acceptable.

    Children and Adolescents 12 to 17 years

    30 mg PO once daily for 4 weeks.

    For the treatment of erosive esophagitis.
    For the initial healing of all grades of erosive esophagitis.
    NOTE: Two 30 mg delayed-release orally disintegrating tablets (SoluTabs) are not interchangable with a single 60 mg delayed-release capsule. The SoluTabs are not approved for the initial treatment of erosive esophagitis.
    Oral dosage (delayed-release capsules only)
    Adults

    60 mg PO once daily for up to 8 weeks.

    Children and Adolescents 12 to 17 years

    60 mg PO once daily for up to 8 weeks.

    For maintenance of healed erosive esophagitis and relief of pyrosis (heartburn).
    Oral dosage
    Adults

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

    Children and Adolescents 12 to 17 years

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

    For the treatment of proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE) in the differential diagnosis of eosinophilic esophagitis (EoE)†.
    Oral dosage
    Adults

    PPI dosing in the range of 20 to 40 mg PO twice daily 30 to 60 minutes before meals has been studied; treat for up to 8 weeks and continue until the time of the follow-up endoscopy and biopsy. For dexlansoprazole, a dose of 60 mg once daily PO should provide similar acid suppression, and is currently under clinical study for EoE. According to guidelines, a PPI trial is central to the differential diagnosis of EoE. If eosinophilia and symptoms persist on repeat endoscopy and biopsy following a PPI trial, then EoE can be formally diagnosed. If symptoms and eosinophilia resolve, then PPI-REE is diagnosed; PPI-REE patients may or may not have underlying GERD. More than one-third of all patients with esophageal eosinophilia on biopsy will respond to a PPI.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

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

    Geriatric

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

    Adolescents

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

    Children

    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.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    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.

    Renal Impairment

    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.

    ADMINISTRATION

    Oral Administration

    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.

    Oral Solid Formulations

    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.

    STORAGE

    Dexilant :
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Kapidex:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Proton pump inhibitors (PPIs) hypersensitivity

    Dexlansoprazole is contraindicated in patients who have shown dexlansoprazole hypersensitivity. Dexlansoprazole is a PPI and should be used with caution in patients with known proton pump inhibitors (PPIs) hypersensitivity. There has been evidence of PPI cross-sensitivity in some sensitive individuals in literature reports. Although rare, occasionally such reactions can be serious (e.g., result in anaphylaxis, angioedema, or acute interstitial nephritis).

    Vitamin B12 deficiency

    Daily treatment with gastric acid-suppressing medication such as dexlansoprazole over a long period of time (e.g., generally > 3 years) may lead to malabsorption of cyanocobalamin and vitamin B12 deficiency. Cases of cyanocobalamin deficiency occurring with acid-suppression therapy have been reported in the literature. One large case-controlled study compared patients with and without an incident diagnosis of vitamin B12 deficiency. A correlation was demonstrated between vitamin B12 deficiency and gastric acid-suppression therapy of > 2 years duration [i.e., proton pump inhibitor (PPI), H2-receptor antagonist]. In addition, a dose-dependant relationship was evident, as larger daily PPI pill counts were more strongly associated with vitamin B12 deficiency. The possibility of cyanocobalamin deficiency should, therefore, be considered if clinical symptoms are observed.

    Hepatic disease

    Compared to patients with normal hepatic function, patients with hepatic disease (moderately impaired hepatic function) had approximately 2 times greater plasma exposure (AUC) of dexlansoprazole after a single 60 mg dose. Consider dosage reduction for patients with moderate hepatic impairment (Child-Pugh class B). No studies have been conducted in patients with severe hepatic impairment (Child-Pugh class C).

    Gastric cancer

    Gastric polyps/fundic gland polyps have been reported during postmarketing surveillance. Patients are usually asymptomatic and fundic gland polyps are identified incidentally on endoscopy. The risk of fundic gland polyps increases with long term proton pump inhibitor (PPI) use, especially beyond one year. Use the shortest duration of PPI therapy appropriate to treat specific condition. Symptomatic response to therapy with dexlansoprazole does not preclude the presence of gastric cancer or other malignancy.

    Bone fractures, osteopenia, osteoporosis

    Use proton pump inhibitors (PPIs) in patients with or who have risk factors for osteoporosis or osteopenia cautiously. PPIs have been associated with a possible increased risk of bone fractures of the hip, wrist, and spine. Epidemiological studies have reported an increased risk of fractures with the use of PPIs; the studies compared claims data of patients treated with PPIs versus individuals who were not using PPIs. The risk of fracture was increased in patients who received high-dose (defined as multiple daily doses or doses greater than those recommended in non-prescription use), and long-term PPI therapy (a year or longer); fractures were primarily observed in adult patients 50 years of age and older. Pre-approval randomized clinical trials (RCTs) of PPIs have not found an increased risk of fractures of the hip, wrist, or spine; however, these RCTs were of shorter study duration (generally 6 months or less). When prescribing PPIs, consider whether a lower dose or shorter duration of therapy would adequately treat the patient's condition. In patients with or at risk for osteopenia or osteoporosis, manage their bone status according to current clinical practice, and ensure adequate vitamin D and calcium supplementation.

    Hypomagnesemia, long QT syndrome

    Daily treatment with a gastric acid-suppressing medication over a long period of time (e.g., 3 months to > 1 year) may lead to hypomagnesemia; cases have been reported in patients taking dexlansoprazole. Generally, hypomagnesemia is corrected with magnesium supplementation; however, in cases where hypomagnesemia is observed during PPI administration, discontinuation of the PPI may also be necessary. Low serum magnesium may lead to serious adverse events such as muscle spasm (tetany), seizures, and irregular heartbeat (arrhythmias). Use PPIs with caution and, if possible, avoid long-term (> 14 days) use in patients with congenital long QT syndrome, as they may be at higher risk for arrhythmias. In pediatric patients, irregular heartbeat may cause fatigue, upset stomach, dizziness, and lightheadedness. For patients expected to be on PPI therapy for a prolonged period of time, it is prudent for clinicians to obtain serum magnesium concentrations prior to initiating PPI therapy as well as throughout treatment. Patients on concomitant medications such as digoxin or diuretics may also require periodic monitoring of serum magnesium.

    Diarrhea, pseudomembranous colitis

    The use of gastric acid suppressive therapy, such as PPIs, may increase the risk of enteric infection by encouraging the growth of gut microflora and increasing susceptibility to organisms including Salmonella, Campylobacter jejuni, Escherichia coli, Clostridium difficile, Vibrio cholerae, and Listeria. A systematic review examined the relationship between PPI use and susceptibility to enteric infections and found enhanced susceptibility for Salmonella infections (adjusted RR range: 4.2—8.3 in 2 studies), Campylobacter (RR 3.5—11.7 in 4 studies) and C. difficile infections (RR 1.2—5.0 in 17 out of 27 studies). In particular, PPI use has been linked to an increased risk of Clostridium difficile–associated diarrhea (CDAD). A diagnosis of CDAD should be considered for patients taking PPIs who develop diarrhea that does not improve. Advise patients to seek immediate care from a healthcare professional if they experience watery stool that does not go away, abdominal pain, and fever while taking PPIs. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. The PPIs, including dexlansoprazole, are recommended for use in combination with certain antibiotics to eradicate Helicobacter pylori. Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents in combination with PPIs.

    Rebound acid hypersecretion

    Studies suggest that long-term PPI therapy is associated with a temporal increase in gastric acid secretion shortly following treatment discontinuation. A similar and well established response has been noted after withdrawal of H2 blockers. Profound gastric acid suppression during PPI therapy leads to a drug-induced reflex hypergastrinemia and subsequent rebound acid hypersecretion. In this hypersecretory state, enterochromaffin-like cell hypertrophy also results in a temporal increase in serum chromogranin A (CgA) levels. It is unclear, however, if this hypersecretory reflex results in clinically significant effects in patients on or attempting to discontinue PPI therapy. A clinically significant effect may lead to gastric acid-related symptoms upon PPI withdrawal and possible therapy dependence. Studies in healthy subjects (H. pylori negative) as well as GERD patients, present conflicting data regarding whether PPI therapy beyond 8-weeks is associated with rebound acid hypersecretion and associated dyspeptic symptoms shortly following PPI cessation. Until more consistent study results shed light on this possible effect, it is prudent to follow current treatment guidelines employing the lowest effective dose, for the shortest duration of time in symptomatic patients. For patients requiring maintenance therapy, consider on demand or intermittent PPI therapy, step down therapy to an H2 blocker, and regularly assess the need for continued gastric suppressive therapy.

    Pregnancy

    There are no adequate and well-controlled studies with dexlansoprazole in pregnant women. 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. However, because animal studies are not always predictive of human response, dexlansoprazole should only be used during pregnancy if clearly indicated. In 2009, a population-based observational cohort study explored a possible link between gastric acid suppressive therapy (e.g., proton pump inhibitors) during pregnancy and a diagnosis of allergic disease or a prescription for asthma or allergy medications in the exposed child. Among the cohort (n = 585,716), 1% of children exposed to gastric acid suppressive drugs in pregnancy received a diagnosis of allergic diease. For developing allergy or asthma, an increased OR of 1.43 and 1.51, respectively, were observed regardless of drug used, time of exposure during pregnancy, and maternal history of disease. Proposed possible mechanisms for a link include: (1) exposure to increased amounts of allergens could cause sensitization to digestion-labile antigens in the fetus; (2) the maternal Th2 cytokine pattern could promote an allergy prone phenotype in the fetus; (3) maternal allergen specific immunoglobulin could cross the placenta and sensitize fetal immune cells to food and airborne allergens. Study limitations were present and confirmation of results are necessary before further conclusions can be drawn from this data. Risk versus benefit should be considered prior to use.

    Breast-feeding

    It is not known whether dexlansoprazole is excreted in human milk. Alternative therapies for consideration include antacids and H2 blockers. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Laboratory test interference

    Administration of dexlansoprazole may result in laboratory test interference, specifically serum chromogranin A (CgA) tests for neuroendocrine tumors, secretin stimulation tests, and urine tests for tetrahydrocannabinol (THC). First, low gastric acidity induced by dexlansoprazole can cause increases in CgA concentrations. Elevated serum CgA levels may be falsely interpreted as a positive result for neuroendocrine tumors. To prevent false positives, temporarily stop dexlansoprazole at least 14 days before assessing CgA concentrations, and consider repeating the test if initial levels are high. If serial test are preformed, ensure the same commercial laboratory is used as reference ranges may vary. Second, dexlansoprazole may cause a hyper-response in gastrin secretion to the secretin stimulation test. This false positive test may suggest gastrinoma. Health care providers are advised to temporarily stop dexlansoprazole at least 30 days prior to performing a secretin stimulation test. Finally, reports have suggested use of dexlansoprazole may cause false positive urine screening tests for THC. If a dexlansoprazole-induced false positive urine screen is suspected, confirm the positive results using an alternative testing method.

    Systemic lupus erythematosus (SLE)

    Use with caution in patients with a history of systemic lupus erythematosus (SLE) as dexlansoprazole has been reported to activate or exacerbate SLE. 

    Geriatric

    According to the Beers Criteria, proton pump inhibitors (PPIs) are considered potentially inappropriate medications (PIMs) for use in geriatric patients due to the risk of Clostridium difficile infection and bone loss/fractures. Avoid use for more than 8 weeks except for high-risk patients (e.g., oral corticosteroids or chronic NSAID use), erosive esophagitis, Barrett's esophagitis, pathological hypersecretory condition, or need for maintenance treatment (e.g., due to failure of drug discontinuation trial or inadequate response to H-2 blockers).[63923] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs); the indication for PPI use should be based on clinical symptoms and/or endoscopic findings. During the use of PPIs to treat or prevent NSAID-induced gastritis or esophagitis, there should be documentation that analgesics with less GI toxicity than NSAIDs have been tried or were not indicated. If a PPI is used for longer than 12 weeks, the clinical rationale and documentation for continued use should support an underlying chronic disease (e.g., GERD) or risk factors (e.g., chronic NSAID use). Monitor for adverse events, including an increased risk of Clostridium difficile colitis.[60742]

    ADVERSE REACTIONS

    Severe

    bezoar / Delayed / 0-2.0
    hematemesis / 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
    vasculitis / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    Stevens-Johnson syndrome / Delayed / 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
    interstitial nephritis / Delayed / Incidence not known

    Moderate

    esophagitis / Delayed / 0-2.0
    dysphagia / Delayed / 0-2.0
    hemorrhoids / Delayed / 0-2.0
    proctitis / Delayed / 0-2.0
    gastritis / Delayed / 0-2.0
    constipation / 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
    goiter / Delayed / 0-2.0
    hypercalcemia / Delayed / 0-2.0
    hypokalemia / Delayed / 0-2.0
    candidiasis / Delayed / 0-2.0
    dyspareunia / Delayed / 0-2.0
    ocular inflammation / Early / 0-2.0
    dysuria / 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
    hyperglycemia / Delayed / Incidence not known
    hypothyroidism / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known
    hypomagnesemia / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    diabetes mellitus / Delayed / Incidence not known
    dehydration / Delayed / Incidence not known
    gout / Delayed / Incidence not known
    hyperlipidemia / Delayed / Incidence not known
    dysphonia / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known

    Mild

    nausea / Early / 2.9-2.9
    halitosis / Early / 0-2.0
    xerostomia / Early / 0-2.0
    dyspepsia / Early / 0-2.0
    anorexia / Delayed / 0-2.0
    appetite stimulation / Delayed / 0-2.0
    eructation / Early / 0-2.0
    rash / Early / 0-2.0
    acne vulgaris / Delayed / 0-2.0
    urticaria / Rapid / 0-2.0
    pruritus / 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
    urinary urgency / Early / 0-2.0
    dysmenorrhea / Delayed / 0-2.0
    ocular irritation / Rapid / 0-2.0
    tinnitus / Delayed / 0-2.0
    menstrual irregularity / Delayed / 0-2.0
    fever / Early / 0-2.0
    chills / Rapid / 0-2.0
    otalgia / Early / 0-2.0
    menorrhagia / Delayed / 0-2.0
    vertigo / Early / 0-2.0
    infection / Delayed / 1.9-1.9
    flatulence / Early / 1.6-1.6
    vomiting / Early / 1.6-1.6
    abdominal pain / Early / 4.0
    headache / Early / 2.0
    diarrhea / Early / 4.8
    gastric polyps / Delayed / Incidence not known
    tenesmus / Delayed / Incidence not known
    folliculitis / Delayed / Incidence not known
    restless legs syndrome (RLS) / Delayed / Incidence not known
    epistaxis / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acalabrutinib: (Major) Avoid the concomitant use of acalabrutinib and proton pump inhibitors (PPI), such as dexlansoprazole; decreased acalabrutinib exposure may occur resulting in decreased acalabrutinib effectiveness. Consider using an antacid or H2-blocker if acid suppression therapy is needed. Separate the administration of acalabrutinib and antacids by at least 2 hours; give acalabrutinib 2 hours before a H2-blocker. Acalabrutinib solubility decreases with increasing pH values. The AUC of acalabrutinib was decreased by 43% when acalabrutinib was coadministered with another PPI for 5 days.
    Acetaminophen; Butalbital: (Major) Avoid coadministration of dexlansoprazole with barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
    Acetaminophen; Butalbital; Caffeine: (Major) Avoid coadministration of dexlansoprazole with barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Major) Avoid coadministration of dexlansoprazole with barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
    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.
    Amobarbital: (Major) Avoid coadministration of dexlansoprazole with barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
    Amphetamine: (Moderate) The use of proton pump inhibitors (PPIs) with amphetamine and/or dextroamphetamine therapy may change the onset of action of these amphetamines due to the increase in gastric pH. The time to maximum concentration (Tmax) of amphetamines is decreased compared to when administered alone, thus increasing amphetamine concentrations and exposure, which may be of particular significance with extended-release dosage forms. Monitor clinical response and adjust if needed. Some extended-release dosage forms of amphetamine or dextroamphetamine salts should not be given with PPIs. The concomitant use of PPIs with some extended-release dosage forms may result in amphetamine dose-dumping.
    Amphetamine; Dextroamphetamine Salts: (Moderate) The use of proton pump inhibitors (PPIs) with amphetamine and/or dextroamphetamine therapy may change the onset of action of these amphetamines due to the increase in gastric pH. The time to maximum concentration (Tmax) of amphetamines is decreased compared to when administered alone, thus increasing amphetamine concentrations and exposure, which may be of particular significance with extended-release dosage forms. Monitor clinical response and adjust if needed. Some extended-release dosage forms of amphetamine or dextroamphetamine salts should not be given with PPIs. The concomitant use of PPIs with some extended-release dosage forms may result in amphetamine dose-dumping.
    Amphetamine; Dextroamphetamine: (Moderate) The use of proton pump inhibitors (PPIs) with amphetamine and/or dextroamphetamine therapy may change the onset of action of these amphetamines due to the increase in gastric pH. The time to maximum concentration (Tmax) of amphetamines is decreased compared to when administered alone, thus increasing amphetamine concentrations and exposure, which may be of particular significance with extended-release dosage forms. Monitor clinical response and adjust if needed. Some extended-release dosage forms of amphetamine or dextroamphetamine salts should not be given with PPIs. The concomitant use of PPIs with some extended-release dosage forms may result in amphetamine dose-dumping.
    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.
    Anticholinergics: (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.
    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.
    Aprepitant, Fosaprepitant: (Minor) Use caution if dexlansoprazole and aprepitant are used concurrently and monitor for an increase in dexlansoprazole-related adverse effects for several days after administration of a multi-day aprepitant regimen. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Dexlansoprazole is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer; substitution of fosaprepitant 115 mg IV on day 1 of the 3-day regimen may lessen the inhibitory effects of CYP3A4. The AUC of a single dose of another CYP3A4 substrate, midazolam, increased by 2.3-fold and 3.3-fold on days 1 and 5, respectively, when coadministered with a 5-day oral aprepitant regimen. After a 3-day oral aprepitant regimen, the AUC of midazolam increased by 25% on day 4, and decreased by 19% and 4% on days 8 and 15, respectively, when given on days 1, 4, 8, and 15. As a single 40-mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.2-fold; the midazolam AUC increased by 1.5-fold after a single 125-mg dose of oral aprepitant. After single doses of IV fosaprepitant, the midazolam AUC increased by 1.8-fold (150 mg) and 1.6-fold (100 mg); less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid coadministration of dexlansoprazole with barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Avoid coadministration of dexlansoprazole with barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
    Atazanavir: (Severe) 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: (Severe) 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.
    Atropine: (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.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (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.
    Atropine; Difenoxin: (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.
    Atropine; Diphenoxylate: (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.
    Atropine; Edrophonium: (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.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Major) Avoid coadministration of dexlansoprazole with barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19. (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.
    Barbiturates: (Major) Avoid coadministration of dexlansoprazole with barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Avoid coadministration of dexlansoprazole with barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19. (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.
    Belladonna; Opium: (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.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (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.
    Benztropine: (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.
    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.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering dexlansoprazole with boceprevir due to an increased potential for dexlansoprazole-related adverse events. If dexlansoprazole dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dexlansoprazole. Dexlansoprazole is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dexlansoprazole plasma concentrations.
    Bortezomib: (Minor) Bortezomib may inhibit CYP2C19 activity at therapeutic concentrations and increase exposure to drugs that are substrates for this enzyme including proton pump inhibitors.
    Bosentan: (Moderate) Monitor for decreased efficacy of dexlansoprazole if coadministration of bosentan is necessary. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Bosentan is a moderate CYP3A4 inducer. The manufacturer of dexlansoprazole recommends avoidance with strong inducers because decreased exposure of dexlansoprazole can occur. Recommendations are not available for concomitant use with moderate inducers of CYP3A4.
    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.
    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.
    Butabarbital: (Major) Avoid coadministration of dexlansoprazole with barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
    Calcium Carbonate; 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.
    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.
    Ceftibuten: (Minor) Coadministration of 150 mg of ranitidine every 12 hours for 3 days increased the ceftibuten Cmax by 23 percent and ceftibuten AUC by 16 percent. Based on this information, increased gastric pH caused by PPIs may possibly affect the kinetics of ceftibuten.
    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.
    Chlordiazepoxide; Clidinium: (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.
    Ciprofloxacin: (Minor) The plasma concentrations of dexlansoprazole may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while dexlansoprazole is a CYP3A4 substrate.
    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.
    Cyanocobalamin, Vitamin B12: (Moderate) Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency.
    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.
    Dasabuvir; Ombitasvir; Paritaprevir; 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.
    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.
    Dexamethasone: (Moderate) Monitor for decreased efficacy of dexlansoprazole if coadministration of dexamethasone is necessary. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Dexamethasone is a moderate CYP3A4 inducer. The manufacturer of dexlansoprazole recommends avoidance with strong inducers because decreased exposure of dexlansoprazole can occur. Recommendations are not available for concomitant use with moderate inducers of CYP3A4.
    Dexmethylphenidate: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release dexmethylphenidate (Focalin XR) have not been studied. Per the manufacturer of extended-release dexmethylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release dexmethylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release dexmethylphenidate.
    Dextroamphetamine: (Moderate) The use of proton pump inhibitors (PPIs) with amphetamine and/or dextroamphetamine therapy may change the onset of action of these amphetamines due to the increase in gastric pH. The time to maximum concentration (Tmax) of amphetamines is decreased compared to when administered alone, thus increasing amphetamine concentrations and exposure, which may be of particular significance with extended-release dosage forms. Monitor clinical response and adjust if needed. Some extended-release dosage forms of amphetamine or dextroamphetamine salts should not be given with PPIs. The concomitant use of PPIs with some extended-release dosage forms may result in amphetamine dose-dumping.
    Dicyclomine: (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.
    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: (Severe) 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.
    Dronedarone: (Moderate) Dronedarone is metabolized by and is an inhibitor of CYP3A. Dexlansoprazole is a substrate for CYP3A4. The concomitant administration of dronedarone and CYP3A substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution.
    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: (Severe) 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: (Severe) 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%.
    Eslicarbazepine: (Moderate) Eslicarbazepine may inhibit the CYP2C19-mediated and induce the CYP3A4-mediated metabolism of dexlansoprazole; both enzymes are involved in the metabolism of proton pump inhibitors (PPIs). It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and PPIs. If eslicarbazepine and PPI must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy, or for signs of PPI side effects.
    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 alcoholic beverages (ethanol) 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.
    Fedratinib: (Minor) The plasma concentrations of dexlansoprazole may be elevated when administered concurrently with fedratinib. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. fedratinib is a moderate CYP3A4 and CYP2C19 inhibitor, while dexlansoprazole is a CYP3A4 and CYP2C19 substrate.
    Flavoxate: (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.
    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%.
    Glycopyrrolate: (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.
    Glycopyrrolate; Formoterol: (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.
    Homatropine; Hydrocodone: (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.
    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.
    Hyoscyamine: (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.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (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.
    Indacaterol; Glycopyrrolate: (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.
    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.
    Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with dexlansoprazole may result in increased serum concentrations of dexlansoprazole. Dexlansoprazole is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple 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 rifampin 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.
    Isoniazid, INH; Rifampin: (Major) Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple 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 rifampin 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.
    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) Because ketoconazole requires an acidic pH for absorption, coadministration of a proton pump inhibitor (PPI) with ketoconazole can cause a notable decrease in the bioavailability of ketoconazole. PPIs have a prolonged duration of action, and staggering their time of administration with ketoconazole by several hours may not prevent the drug interaction. An alternative imidazole antifungal should be chosen if any of these gastrointestinal medications are required. If these drugs must be coadministered, administer ketoconazole tablets with an acidic beverage and closely monitor for breakthrough infection.
    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.
    Lefamulin: (Minor) The plasma concentrations of dexlansoprazole may be elevated when administered concurrently with oral lefamulin. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Dexlansoprazole is a CYP3A4 substrate; oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin.
    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.
    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.
    Luliconazole: (Minor) Theoretically, luliconazole may increase the side effects of dexlansoprazole, which is a CYP2C19 and CYP3A4 substrate. Monitor patients for adverse effects of dexlansoprazole, such as electrolyte changes. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
    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.
    Mepenzolate: (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.
    Mephobarbital: (Major) Avoid coadministration of dexlansoprazole with barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
    Mesalamine, 5-ASA: (Major) The dissolution of the coating on mesalamine extended-release capsules (Apriso) and the delayed-release tablets (Lialda) is dependent on pH. Avoid coadministration with drugs that raise gastric pH like proton pump inhibitors.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (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.
    Methohexital: (Major) Avoid coadministration of dexlansoprazole with barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
    Methotrexate: (Major) Use caution when administering high-dose methotrexate to patients receiving proton pump inhibitors (PPIs); a temporary withdrawal of the PPI should be considered in some patients receiving high-dose methotrexate. Case reports and published population pharmacokinetic studies suggest that concomitant use of some PPIs such as omeprazole, pantoprazole, or esomeprazole with methotrexate primarily at high dose may elevate and prolong serum methotrexate concentrations and/or its metabolite hydroxymethotrexate, which may lead to methotrexate toxicities. In two of these cases, delayed methotrexate elimination was observed when high-dose methotrexate was coadministered with PPIs but was not observed when methotrexate was coadministered with ranitidine. However, no formal drug interaction studies of methotrexate with ranitidine have been conducted. Among adults who received high-dose methotrexate (median dose of 3500 mg/m2, range of 1000-5000 mg/m2), coadministration of PPIs such as omeprazole, lansoprazole, or rabeprazole was identified as a risk factor for delayed methotrexate elimination with an OR of 2.65 (95% confidence interval 1.036.82). The interaction may be partially explained by the inhibitory effects of PPIs on breast cancer resistance protein (BCRP, ABCG2) -mediated methotrexate transport. Altered methotrexate elimination may not be present or problematic among patients who receive lower methotrexate doses. For example, coadministration of lansoprazole 30 mg daily and naproxen 500 mg twice daily for 7 days to recipients of stable oral methotrexate doses (7.515 mg/week) for a minimum of 3 months did not alter the pharmacokinetic profile of either methotrexate or 7-hydroxymethotrexate. Specifically, the peak plasma concentration and area under the plasma concentration-time curve of methotrexate and 7-hydroxymethotrexate were within the 0.80 to 1.25 boundaries.
    Methscopolamine: (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.
    Methylphenidate: (Minor) The effects of gastrointestinal pH alterations on the absorption of extended-release methylphenidate (Ritalin LA) have not been studied. Per the manufacturer of extended-release methylphenidate, the modified release characteristics are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of extended-release methylphenidate, resulting in reduced or increased absorption. Patients receiving a PPI should be monitored for adverse effects and reduced therapeutic efficacy of extended-release methylphenidate.
    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.
    Modafinil: (Minor) Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Modafinil induces hepatic cytochrome P-450 enzyme CYP3A4 but significantly inhibits CYP2C19; both of these enzymes are responsible for the metabolism of PPIs. It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. If modafinil 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, or for signs of PPI side effects.
    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.
    Octreotide: (Minor) The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents, such as octreotide. Proton pump inhibitors inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
    Ombitasvir; Paritaprevir; 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.
    Oritavancin: (Moderate) Coadministration of oritavancin and dexlansoprazole may result in increases or decreases in dexlansoprazole exposure and may increase side effects or decrease efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP3A4 and CYP2C19. Oritavancin weakly induces CYP3A4, while weakly inhibiting CYP2C19. If these drugs are administered concurrently, monitor the patient for signs of toxicity or lack of efficacy.
    Oxybutynin: (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.
    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.
    Pentobarbital: (Major) Avoid coadministration of dexlansoprazole with barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
    Phenobarbital: (Major) Avoid coadministration of dexlansoprazole with barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
    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.
    Ponatinib: (Major) Ponatinib displays pH-dependent aqueous solubility; therefore, concomitant use of ponatinib and proton-pump inhibitors, such as dexlansoprazole, may result in decreased bioavailability and plasma exposure of ponatinib. Avoid concomitant use of ponatinib with proton-pump inhibitors unless the benefit outweighs the possible risk of ponatinib underexposure. If the use of both agents is necessary, monitor patients for signs of reduced efficacy.
    Posaconazole: (Major) The concurrent use of posaconazole 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 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 barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
    Propantheline: (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.
    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.
    Rifabutin: (Major) Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple 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 rifampin 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.
    Rifampin: (Major) Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple 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 rifampin 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.
    Rifamycins: (Major) Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple 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 rifampin 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.
    Rifapentine: (Major) Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple 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 rifampin 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.
    Rilpivirine: (Severe) 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.
    Scopolamine: (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.
    Secobarbital: (Major) Avoid coadministration of dexlansoprazole with barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
    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.
    Simeprevir: (Minor) Simeprevir, a mild intestinal CYP3A4 inhibitor, may increase the side effects of dexlansoprazole, which is a CYP3A4 substrate. Monitor patients for adverse effects of dexlansoprazole, such as electroyle changes.
    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.
    St. John's Wort, Hypericum perforatum: (Major) Coadministration of St. John's Wort, Hypericum perforatum (300 mg three times daily) for 14 days with a one time dose of omeprazole (20 mg) on day 15 resulted in decreased omeprazole plasma concentrations in healthy subjects. Omeprazole AUC was reduced by approximately 40% in both poor and extensive metabolizers of CYP2C19. The clinical significance of this interaction is not clear; however, due to variations in the amounts of active ingredient in herbal products, the magnitude of this interaction and the resultant clinical effect may vary. St. John's Wort induces both CYP3A4 and CYP2C19 dependent metabolism of omeprazole. Since, proton pump inhibitors (PPIs) are primary substrates of the CYP2C19 enzyme, patients taking St. John's Wort concomitantly with a PPI should be monitored for PPI efficacy.
    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) Concomitant administration of dexlansoprazole and tacrolimus may increase serum concentrations of tracrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19. Monitor tacrolimus whole blood concentrations, and adjust dose as needed to maintain therapeutic drug concentrations.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering dexlansoprazole with telaprevir due to an increased potential for dexlansoprazole-related adverse events. If dexlansoprazole dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dexlansoprazole. Dexlansoprazole is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dexlansoprazole plasma concentrations.
    Telithromycin: (Minor) Concentrations of dexlansoprazole may be increased with concomitant use of telithromycin. Dexlansoprazole is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and dexlansoprazole is necessary, as the systemic exposure of dexlansoprazole may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of dexlansoprazole; consider increasing the dose of dexlansoprazole if necessary. Dexlansoprazole is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    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.
    Thiopental: (Major) Avoid coadministration of dexlansoprazole with barbiturates because it may result in decreased efficacy of dexlansoprazole. Dexlansoprazole is metabolized by CYP2C19 and CYP3A4. Barbiturates induce CYP3A4 and CYP2C19.
    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.
    Trihexyphenidyl: (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.
    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.
    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) Omeprazole (CYP2C19 inhibitor) can prolong the elimination of warfarin, particularly R-warfarin which is partially metabolized by CYP2C19. The combined use of omeprazole and warfarin has been associated with reports of increased INR and prothrombin time (PT). In addition, post-marketing reports of the combination of esomeprazole and warfarin have indicated elevations in PT. There have been reports of increased International Normalized Ratio (INR) and prothrombin time in patients receiving other proton pump inhibitors (PPIs) (including esomeprazole, lansoprazole, rabeprazole, and pantoprazole and warfarin concomitantly. It is prudent to monitor the INR more closely if these agents are combined with warfarin.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies with dexlansoprazole in pregnant women. 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. However, because animal studies are not always predictive of human response, dexlansoprazole should only be used during pregnancy if clearly indicated. In 2009, a population-based observational cohort study explored a possible link between gastric acid suppressive therapy (e.g., proton pump inhibitors) during pregnancy and a diagnosis of allergic disease or a prescription for asthma or allergy medications in the exposed child. Among the cohort (n = 585,716), 1% of children exposed to gastric acid suppressive drugs in pregnancy received a diagnosis of allergic diease. For developing allergy or asthma, an increased OR of 1.43 and 1.51, respectively, were observed regardless of drug used, time of exposure during pregnancy, and maternal history of disease. Proposed possible mechanisms for a link include: (1) exposure to increased amounts of allergens could cause sensitization to digestion-labile antigens in the fetus; (2) the maternal Th2 cytokine pattern could promote an allergy prone phenotype in the fetus; (3) maternal allergen specific immunoglobulin could cross the placenta and sensitize fetal immune cells to food and airborne allergens. Study limitations were present and confirmation of results are necessary before further conclusions can be drawn from this data. Risk versus benefit should be considered prior to use.

    It is not known whether dexlansoprazole is excreted in human milk. Alternative therapies for consideration include antacids and H2 blockers. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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.

    Oral Route

    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.