lansoprazole (Rx, OTC)

1-10%

Headache (3-7%)

Diarrhea (1-5%)

Constipation (1-5%)

Nausea (1-3%)

Abdominal pain (1-3%)

<1%

Anxiety

Angina

Palpitations

Syncope

Edema

Anorexia

Dry mouth

Tenesmus

Flatulence

Melena

Myalgia

Tinnitus

Allergic reaction

Postmarketing Reports

Bone fracture

Fundic gland polyps

Acute tubulointerstitial nephritis

Contraindications

Hypersensitivity to lansoprazole or other proton pump inhibitors

Coadministration with rilpivirine-containing products

Cautions

Proton pump inhibitors (PPIs) are possibly associated with increased incidence of Clostridium difficile-associated diarrhea (CDAD); consider diagnosis of CDAD for patients taking PPIs who have diarrhea that does not improve

Liver disease may require dosage reduction

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) reported with PPIs; avoid using for longer than medically indicated; discontinue if signs or symptoms consistent with CLE or SLE are observed and refer patient to specialist

Published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine, particularly with prolonged (>1 yr), high-dose therapy

Decreased gastric acidity increases serum chromogranin A (CgA) levels and may cause false-positive diagnostic results for neuroendocrine tumors; temporarily discontinue PPIs before assessing CgA levels

Hypomagnesemia may occur with prolonged use (ie, >1 year); adverse effects may result and include tetany, arrhythmias, and seizures; in 25% of cases reviewed, magnesium supplementation alone did not improve low serum magnesium levels and the PPI had to be discontinued

PPIs may decrease the efficacy of clopidogrel by reducing the formation of the active metabolite

Relief of symptoms does not eliminate the possibility of a gastric malignancy

Therapy increases risk of Salmonella, Campylobacter, and other infections

Acute interstitial nephritis reported in patients taking proton pump inhibitors; discontinue therapy if interstitial nephritis develops

Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin

May elevate and/or prolong serum concentrations of methotrexate and/or its metabolite when administered concomitantly with PPIs, possibly leading to toxicity; consider a temporary withdrawal of PPI therapy with high dose methotrexate administration

SoluTab dosage form contains phenylalanine, a component of aspartame, which can be harmful to patients with phenylketonuria (PKU); before prescribing lansoprazole to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including the SoluTab dosage form

Some dosage forms contain benzyl alcohol, which has been associated with gasping syndrome in the neonate; avoid or use dosage forms containing benzyl alcohol with caution in neonates

PPI therapy is associated with increased risk of fundic gland polyp; risk increases with long-term use >1 year; patient may be asymptomatic; problem usually identified incidentally on endoscopy; use shortest duration of therapy appropriate to condition being treated

If patient taking a prescription drug, the patient should ask a doctor or a pharmacist whether acid reducers can be taken concomitantly with it

Acute tubulointerstitial nephritis (TIN) reported in patients taking PPIs; may occur at any point during PPI therapy; patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia); in reported case series, some patients were diagnosed on biopsy and in absence of extra-renal manifestations (eg, fever, rash or arthralgia); discontinue therapy and evaluate patients with suspected acute TIN

Pregnancy

Available data from published observational studies overall do not indicate an association of adverse pregnancy outcomes with lansoprazole treatment; estimated background risk of major birth defects and miscarriage for the indicated populations are unknown

Available data from published observational studies failed to demonstrate an association of adverse pregnancy-related outcomes and lansoprazole use; methodological limitations of these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy

Not recommended in pediatric patients <2 years; nonclinical studies in juvenile rats with lansoprazole have demonstrated adverse effect of heart valve thickening

No adverse effects on embryo-fetal development occurred in studies performed in pregnant rats at oral lansoprazole doses up to 150 mg/kg/day (40 times the recommended human dose [30 mg/day] based on body surface area) administered during organogenesis and pregnant rabbits at oral lansoprazole doses up to 0 mg/kg/day (16 times the recommended human dose based on body surface area) administered during organogenesis

Lactation

There is no information regarding presence of lansoprazole in human milk, effects on breastfed infant, or on milk production; however, lansoprazole and its metabolites are present in rat milk; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from treatment or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Proton pump inhibitor; binds to H+/K+-exchanging ATPase (proton pump) in gastric parietal cells, resulting in suppression of basal and stimulated acid secretion

Absorption

Bioavailability: 81-91%; decreased 50-70% if given 30 min after meals

Peak plasma time: 1.7 hr; food increases time to 3.7 hr

Duration (at steady state): >24 hr (PUD, esophagitis); 40 hr (Zollinger-Ellison syndrome)

AUC: Food decreases AUC by 50%

Onset

• Gastric acid suppression: 1-3 hr
• PUD: 1 week (initial); 4-8 days (peak)
• Esophagitis: 1-4 weeks (initial); 8 weeks (peak)

Distribution

Protein bound: 97-99%

Vd: 14-18 L

Metabolism

Metabolized by hepatic CYP2C19; slow metabolizers are deficient in CYP2C19 enzyme and can have plasma concentration increase of 5-fold or higher

Gastric parietal cells: Acidic pH converts lansoprazole to its active sulfenamide metabolites

Active metabolites: Cyclic sulfenamide and disulfide metabolite

Inactive metabolites: 5-hydroxy-lansoprazole, sulfide metabolite, omeprazole sulfone, sulfone metabolite, hydroxysulfide metabolite, hydroxysulfone metabolite

Enzymes inhibited: CYP2C19

Elimination

Half-life: 0.9-1.5 hr

Dialyzable: No

Total renal clearance: 517 mL/min

Total body clearance: 0.7 L/hr/kg

Excretion: feces (bile), 67%; urine, 33%

Oral Administration

Administer before meals

Contains enteric coated granules (acid labile); do not chew or crush; swallow capsule/tablet whole; do not chew, crush, or split

Do not chew orally disintegrating tablets

Powder for oral suspension: dissolve packet contents in 30 mL of water; do not use any other liquid; stir well and drink immediately

IV Preparation

Inject 5 mL sterile water for injection (SWI) into vial and gently dissolve to obtain a 6 mg/mL solution; can be stored at 77°F (25°C) for 1 hr

Dilute in 50 mL NS, LR, or D5W; resulting solution can be stored at 77°F (25°C) for 24 hr (NS, LR) or 12 hr (D5W); refrigeration not necessary.

Alternatively, can be reconstituted directly into 50 mL NS, LR, or D5W using Baxter's MINI-BAG Plus Container

Prime in-line filter as directed in manufacturer's package insert

IV Administration

In-line filter must be used (supplied)

Administer over 30 min

Flush IV line with NS, LR, or D5W before and after use

Do not administer with other drugs