Dexlansoprazole

No occurrences of enterochromaffin-like (ECL) cell carcinoids, dysplasia, or neoplasia (such as those seen in studies of rodents exposed to lansoprazole) have been reported in humans.

Use of proton pump inhibitors (PPIs) may increase risk of CDAD, especially in hospitalized patients; consider CDAD diagnosis in patients with persistent diarrhea that does not improve. Use the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated.

Has been reported as new onset or exacerbation of existing autoimmune disease; most cases were cutaneous lupus erythematosus (CLE), most commonly, subacute CLE (occurring within weeks to years after continuous therapy). Systemic lupus erythematosus (SLE) is less common (typically occurs within days to years after initiating treatment) and occurred primarily in young adults up to elderly patients. Discontinue therapy if signs or symptoms of CLE or SLE occur and refer to specialist for evaluation; most patients improve 4 to 12 weeks after discontinuation of dexlansoprazole.

Increased incidence of osteoporosis-related bone fractures of the hip, spine, or wrist may occur with PPI therapy. Patients on high-dose (multiple daily doses) or long-term therapy (≥1 year) should be monitored. Use the lowest effective dose for the shortest duration of time, use vitamin D and calcium supplementation, and follow appropriate guidelines to reduce risk of fractures in patients at risk.

Reported rarely, usually with prolonged PPI use of ≥3 months (most cases >1 year of therapy). May be symptomatic or asymptomatic; severe cases may cause tetany, seizures, and cardiac arrhythmias. Consider obtaining serum magnesium concentrations prior to beginning long-term therapy, especially if taking concomitant digoxin, diuretics, or other drugs known to cause hypomagnesemia; and periodically thereafter. Hypomagnesemia may be corrected by magnesium supplementation, although discontinuation of dexlansoprazole may be necessary; magnesium levels typically return to normal within 1 week of stopping.

Acute interstitial nephritis has been observed in patients taking PPIs; may occur at any time during therapy and is generally due to an idiopathic hypersensitivity reaction. Discontinue if acute interstitial nephritis develops.

Prolonged treatment (≥2 years) may lead to vitamin B12 malabsorption and subsequent vitamin B12 deficiency. The magnitude of the deficiency is dose related and the association is stronger in females and those younger in age ( Disease-related concerns:

Relief of symptoms does not preclude the presence of a gastric malignancy.

Use of PPIs may increase risk of these infections.

Patients with moderate hepatic impairment (Child-Pugh class B) may require dosage reductions; use is not recommended in patients with severe hepatic impairment (Child-Pugh class C). Concurrent drug therapy issues:

PPIs may diminish the therapeutic effect of clopidogrel, thought to be due to reduced formation of the active metabolite of clopidogrel. The manufacturer of clopidogrel recommends either avoidance of both omeprazole (even when scheduled 12 hours apart) and esomeprazole or use of a PPI with comparatively less effect on the active metabolite of clopidogrel (eg, pantoprazole). Although lansoprazole exhibits the most potent CYP2C19 inhibition in vitro (Li 2004; Ogilvie 2011), an in vivo study of extensive CYP2C19 metabolizers showed less reduction of the active metabolite of clopidogrel when administered with lansoprazole/dexlansoprazole compared to esomeprazole/omeprazole (Frelinger 2012). In contrast to these warnings, others have recommended the continued use of PPIs, regardless of the degree of inhibition, in patients with a history of GI bleeding or multiple risk factors for GI bleeding who are also receiving clopidogrel since no evidence has established clinically meaningful differences in outcome; however, a clinically significant interaction cannot be excluded in those who are poor metabolizers of clopidogrel (Abraham 2010; Levine 2011). The manufacturer of dexlansoprazole states that no dosage adjustment is necessary for clopidogrel when used concurrently with approved doses.

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Other warnings/precautions:

Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acid; may cause false-positive results in diagnostic investigations for neuroendocrine tumors. Temporarily stop dexlansoprazole treatment at least 14 days before CgA test; if CgA level is high, repeat test to confirm. Use same commercial laboratory for testing to prevent variable results.