General Administration Information
For storage information, see specific product information within the How Supplied section.
-Administer dosage 30 minutes prior to meal whenever possible. A once-daily dosage is usually administered prior to breakfast. The presence of a meal in the stomach decreases the bioavailability by about 50-70%. Antacids were used concomitantly with lansoprazole in clinical trials and can cause a slight reduction in bioavailability.
Oral Solid Formulations
-Delayed-release capsules: Swallow delayed-release capsules intact; do not chew or crush. For patients with difficulty swallowing, the capsules may be opened and the contents sprinkled on 1 tablespoonful (15 ml) of either applesauce, Ensure pudding, yogurt, cottage cheese, or strained pears. Do not crush the capsule contents into the food. Swallow immediately. Do not chew the medication. Do not prepare doses before the time of administration. Alternatively, the capsule may be emptied into a small volume of either apple juice, orange juice, or tomato juice (60 ml, approximately 2 ounces), mixed briefly and swallowed immediately. To ensure complete delivery of the dose, the glass should be rinsed with two or more volumes of juice and the contents swallowed immediately.
-Delayed-release disintegrating tablets: Place on the tongue and allow to disintegrate until the particles can be swallowed. The tablet will disintegrate rapidly (< 1 minute). Do not cut, chew, or crush the tablets. For administration via an oral syringe, the tablet can be dissolved in water (4 ml for 15 mg tablet, 10 ml for 30 mg tablet) and should be administered within 15 minutes.
-Patients with a nasogastric tube: Prevacid capsules or disintegrating tablets can be administered via a nasogastric tube. Capsules: Open the capsule and mix the intact granules in 40 ml of apple juice and inject through the nasogastric tube into the stomach. After administration, flush the nasogastric tube with additional apple juice to clear the tube. Disintegrating tablets: Dissolve tablet in water (4 ml for 15 mg tablet, 10 ml for 30 mg tablet) and administer within 15 minutes. After administration, flush the tube to clear it. Of note, Teva's lansoprazole delayed-release orally disintegrating tablet (ODT) has clogged and blocked oral syringes and feeding tubes, including both gastric and jejunostomy types, when the drug is administered as a suspension through these devices. If alternatives exist, the Teva lansoprazole delayed-release ODT product should not be administered through an oral syringe or feeding tube.
Oral Liquid Formulations
-Delayed-release oral suspension: Packets containing the enteric-coated granules (15 or 30 mg doses) are mixed with 2 tablespoonfuls (30 ml) of water to form a strawberry-flavored suspension intended for immediate administration after mixing. Do not use with other liquids or foods. Stir well and drink immediately. Do not crush or chew the granules. If any material remains after drinking, add more water, stir, and drink immediately.
Extemporaneous preparation of oral suspension ('simplified lansoprazole suspension' or SLS):
-Empty the contents of one 30 mg lansoprazole capsule into an empty 15 ml syringe with needle in place (plunger removed). Then, replace the plunger and uncap the needle. Withdraw 10 ml of sodium bicarbonate 8.4% (1 mEq/ml) solution from a sodium bicarbonate vial. Gently shake syringe for 10 to 15 minutes, until the granules dissolve and a white suspension of lansoprazole is obtained.
-Extended stability data are not available; it is recommended that SLS be used immediately following preparation.
Significant elevations in serum gastrin have been reported with lansoprazole and is consistent with the effects of other PPIs; this effect may be dose-related. Although not specifically studied in patients receiving lansoprazole, the risk of carcinoid tumors during therapy with proton pump inhibitors is low based on cumulative safety experience. Monitoring of serum gastrin levels during PPI therapy is generally not necessary.
Although prolonged hypergastrinemia has been associated with gastric tumors, a long-term study of lansoprazole for the treatment of Zollinger-Ellison syndrome did not reveal evidence to suggest that lansoprazole was implicated in tumor progression noted in two (10%) patients. Both patients already had extensive metastatic disease.
The safety profile of lansoprazole is similar in adults, children, and adolescents 1 to 17 years old. Adverse reactions reported during oral lansoprazole therapy (various dosages) in Phase 2 or Phase 3 clinical trials were primarily related to the GI tract. Constipation has been reported in controlled oral lansoprazole trials compared to placebo (1% vs 0.4%, respectively). In children 1 to 11 years old, the most frequent side effect was constipation (5%). Abdominal pain has been reported in controlled trials of oral lansoprazole compared to placebo (2.1% vs 1.2%), 5% in a trial including 87 adolescent patients, and less frequently (less than 1%) in IV lansoprazole trials. Nausea was reported in 1.3% of patients receiving lansoprazole (vs 1.2% receiving placebo) and in 3% of adolescent patients. Other GI related adverse events such as duodenitis, epigastric discomfort, esophageal disorder, hunger, hiatal hernia, and impaired gastric emptying were reported in a study where patients took either a COX-2 inhibitor or lansoprazole and naproxen. Other GI adverse events occurring in less than 1% of patients receiving lansoprazole during clinical trials include: abnormal stools, anorexia, appetite stimulation, bezoar, dysgeusia, dyspepsia, dysphagia, enlarged abdomen, enteritis, eructation, esophageal stenosis, esophageal ulceration, esophagitis, flatulence, gastritis, gastroenteritis, gastrointestinal anomaly, gastrointestinal disorder, GI bleeding (positive fecal occult blood), glossitis, gum hemorrhage, halitosis, hematemesis, hypersalivation, increased gastrin levels, melena, mouth ulceration, gastrointestinal moniliasis, rectal disorder, stomatitis, stool discoloration, tenesmus, thirst, tongue disorder, ulcerative colitis, ulcerative stomatitis, vomiting, and xerostomia. Gastric polyps/fundic gland polyps have been reported during postmarketing surveillance.
During lansoprazole clinical evaluation, headache was reported in 3% of patients aged 1-11 years and in 7% of patients aged 12-17 years. In placebo-controlled trials (n = 3791), headache was reported in > 1% of patients taking oral lansoprazole and 1% of patients receiving the IV formulation. In patients being treated for H. pylori, headache was reported in 6% of patients receiving lansoprazole plus amoxicillin and clarithromycin triple therapy and in 7% of patients receiving lansoprazole and amoxicillin dual therapy. Other nervous system adverse reactions reported in <1% of patients during clinical evaluation of lansoprazole include: abnormal dreams, abnormal vision, agitation, amblyopia, amnesia, anxiety, apathy, confusion, dementia, depersonalization, depression, diplopia, dizziness, drowsiness, emotional lability, hallucinations, hemiplegia, hostility aggravated, hyperkinesis, hypertonia, hypoesthesia, insomnia, migraine, nervousness, neurosis, paresthesias, parosmia, seizures, sleep disorder, thinking abnormality, tremor, vertigo, and visual field defect. During post-marketing surveillance, speech disorder was also reported.
Cholelithiasis (<1%), hepatoxicity, hyperbilirubinemia, and elevated hepatic enzymes (increased AST, ALT, alkaline phosphatase, and GGTP) have been reported during lansoprazole therapy. In controlled clinical trials, 0.4% (4/978) placebo patients and 0.4% (11/2677) lansoprazole patients had hepatic enzyme elevations > 3 times the upper limit of the normal range at the end of the study, but without evidence of jaundice. Pancreatitis has been reported post-marketing, but causal association and frequency are unknown.
Hematological adverse reactions that have been reported in < 1% of patients receiving lansoprazole included anemia, hemolysis, and lymphadenopathy. During post-marketing surveillance, agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic purpura (TTP) were also reported. In addition, the following laboratory parameter alterations were also reported as adverse events during clinical evaluation: abnormal RBC, increased globulins, increased/decreased/abnormal platelets, increased/decreased/abnormal WBC, eosinophilia, hemoglobin decreased, and hyperuricemia. Generally, long-term (e.g., >= 2-3 years) treatment with acid-suppressing agents can lead to malabsorption of vitamin B12 (cyanocobalamin). In a study of healthy adult volunteers, it was shown that omeprazole caused a significant reduction in cyanocobalamin absorption. In a large case-controlled study, adult patients with and without an incident diagnosis of vitamin B12 deficiency (n = 25,956 and 184,199, respectively) were compared, and a correlation between vitamin B12 deficiency and gastric acid-suppression therapy was found. Receipt of >= 2 years of a proton pump inhibitor or H2-receptor antagonist was associated with an increased risk for vitamin B12 deficiency. A dose-dependent relationship was evident, as daily doses > 1.5 PPI pills/day were more strongly associated with vitamin B12 deficiency compared to daily doses < 0.75 pills/day. The precise risk in pediatric patients has not been defined. It may be prudent to monitor patients for signs of pernicious anemia. Neurological manifestations of pernicious anemia can occur in the absence of hematologic changes.
During clinical evaluation, rash (unspecified) was reported in <1% of patients receiving oral lansoprazole and in 1% of patients receiving the IV formulation. Other dermatological reactions reported in < 1% of lansoprazole-treated patients included: acne vulgaris, allergic reaction, alopecia, contact dermatitis, diaphoresis, fixed eruption, hair disorder, maculopapular rash, nail disorder, pruritus, skin carcinoma, skin disorder, urticaria, and xerosis. Specific dermatological reactions reported during post-marketing surveillance include: anaphylactoid reactions, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis (some fatal).
During trials of intravenously administered lansoprazole, injection site reaction including injection site pain was reported in 1% of patients.
Colitis and ulcerative colitis have been reported among events occurring in < 1% of oral lansoprazole-treated patients during clinical trials. In addition, several case reports and case series have suggested a link between lansoprazole and the onset of microscopic colitis. Reports and subsequent histological confirmation of both collagenous colitis and lymphocytic colitis, two distinct forms of microscopic colitis, have been observed in adult patients treated with lansoprazole. One case series included six adult patients who developed microscopic colitis after a formulary switch to lansoprazole from omeprazole. Upon lansoprazole discontinuation, associated loose stools resolved. The mechanism of this rare adverse reaction is not clear; however, an idiosyncratic immune reaction to lansoprazole is suspected. Because small changes in the structures of PPIs may elicit different immunological responses, it is difficult to predict if this adverse effect can be expected with other PPIs. Until more is known about the association between lansoprazole and microscopic colitis, clinicians should advise patients to report prolonged watery loose stools and lansoprazole discontinuation or substitution should be considered in these patients.
Adverse events affecting the respiratory tract were reported in less than 1% of patients or subjects who received lansoprazole in clinical trials and include: asthma/bronchospasm, bronchitis, cough (increased), dyspnea, epistaxis, flu syndrome, hemoptysis, hiccups, laryngeal neoplasia, lung fibrosis, pharyngitis, pleural disorder, pneumonia, respiratory disorder (unspecified), upper respiratory inflammation/infections, rhinitis, sinusitis, and stridor. Gastric acid suppression with proton pump inhibitors (PPIs) has been associated with an increased risk of infection in pediatric patients. A prospective, multi-center study in previously healthy infants and young children found an increased risk of pneumonia (OR: 6.39; 95% CI = 1.38-29.7) and acute gastroenteritis (OR: 3.58; 95% CI = 1.87-6.86) in patients receiving gastric acid inhibitors (n = 91) compared to controls (n = 95). Another study in critically ill pediatric patients (n = 60) did not find an increased incidence of ventilator-associated pneumonia in patients receiving acid-suppression therapy compared to those not receiving treatment. Until more is known about the relationship between acid-suppression and pneumonia, clinicians are encouraged to carefully select patients before empirically initiating acid-suppressive therapy with H2-blockers or PPIs. A causal relationship between the use of lansoprazole and pneumonia has not been established. Increasing evidence in adults suggests a link between acid-suppression therapy and pneumonia (community- and hospital-acquired). Several mechanisms have been proposed to account for this association. One such mechanism states that gastric pH serves as a barrier against pathogenic colonization of the gastrointestinal tract. An increase in gastric pH allows for bacterial and viral invasion which, in theory, can precipitate respiratory infections. Another proposed mechanism accounts for the role that gastric acid may have on stimulating the cough reflex that allows for the clearing of infectious agents from the respiratory tract. Finally, the fact that acid-suppressive therapy may impair white blood cell function, which in turn may lead to a depressed immune response to an infection, is listed among possible mechanisms.
The following urogenital reactions have been reported in less than 1% of patients during lansoprazole clinical trials: dysmenorrhea, dysuria, increased urinary frequency, kidney calculus, kidney pain, leukorrhea, menorrhagia, menstrual irregularity, pelvic pain, penis disorder, polyuria, testis disorder, urethral pain, urinary retention, urinary tract infection, urinary urgency, urination impaired, and vaginitis. The following laboratory parameter alterations were also reported as adverse events during clinical evaluation of oral lansoprazole: albuminuria (proteinuria), crystal urine present (crystalluria), glycosuria, hematuria, and increased creatinine. In a study where patients took either a COX-2 inhibitor or lansoprazole and naproxen, renal impairment was reported. Urinary retention has been reported postmarketing. Acute tubulo-interstitial nephritis (AIN or TIN) has been observed in patients taking PPIs, including lansoprazole, and 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 the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue lansoprazole and evaluate patients with suspected acute AIN.
Cutaneous lupus erythematosus (CLE), systemic lupus erythematosus (SLE), and lupus-like symptoms have occurred in patients taking PPIs, including lansoprazole. Both exacerbation and new onset of existing autoimmune disease have be reported, with the majority of PPI-induced lupus erythematosus cases being CLE. Subacute CLE (SCLE) is the most common form of CLE reported in patients treated with PPIs, occurring within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Histological findings were usually observed without organ involvement. SLE is less commonly reported; PPI associated SLE is generally milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from infants to the elderly. Most patients presented with rash; however, arthralgia and cytopenia were also reported. Do not administer PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE occur, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks; serological testing (ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations.
During clinical evaluation of oral lansoprazole the following musculoskeletal adverse events were reported in < 1 % of the patient population: arthralgia, arthritis, back pain, bone disorder, joint disorder, leg muscle cramps, musculoskeletal pain, myalgia, myasthenia, neck pain, neck rigidity, and synovitis. Myositis has been reported in post-marketing experience with lansoprazole. Proton pump inhibitors (PPIs) have been associated with a possible increased risk of bone fractures of the hip, wrist, and spine. There have been six epidemiological studies that 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. Depending on the study, exposure to PPIs ranged between 1-12 years. The emergence of fractures varied among studies; one study reported an increase in fractures with use of PPIs in the previous year and another study found an increase after 5-7 years of PPI use. Alternatively, in another epidemiological study with similar study design, a relationship between PPI use and fractures was not established; the study population did not have major risk factors for fracture at study entry. It should be noted that randomized clinical trials (RCTs) of PPIs have not found an increased risk of fractures of the hip, wrist, or spine; some limitations of these RCTs were study duration (generally six months) and insufficient information on effects of higher than recommended doses. Until more data are available, 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 osteoporosis, manage their bone status according to current clinical practice, and ensure adequate vitamin D and calcium supplementation.
Cases of hypomagnesemia have been reported in association with prolonged (3 months to > 1 year) proton pump inhibitor (PPI) use, including lansoprazole. Generally, hypomagnesemia is corrected with magnesium supplementation; however, in cases where hypomagnesia 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). 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.
Other miscellaneous adverse events reported in <1% of patients during clinical evaluation of lansoprazole include: asthenia, avitaminosis, blepharitis, blurred vision, breast enlargement, breast tenderness, candidiasis, carcinoma, cataracts, chills, conjunctivitis, dehydration, diabetes mellitus, dry eyes/xerophthalmia, ear/eye disorder, fever, glaucoma, goiter, gout, gynecomastia, hearing loss, hyperglycemia, hypoglycemia, hypothyroidism, malaise, mastalgia, ocular pain, otitis media, photophobia, ptosis, retinal degeneration/disorder, tinnitus, weight gain, and weight loss. In a study where patients took either a COX-2 inhibitor or lansoprazole and naproxen, reported events included contusion, fatigue, hoarseness, and metaplasia. In addition, the following laboratory parameter alterations were also reported as adverse events during clinical evaluation of oral lansoprazole: abnormal AG ratio, hyperkalemia, increased/decreased electrolytes, and increased glucocorticoids.
Cardiovascular adverse events reported in < 1% of patients during lansoprazole clinical trials included: angina, arrhythmia exacerbation, bradycardia, cardiospasm, cerebrovascular accident/cerebral infarction (stroke), chest pain (unspecified), edema, hypertension, hypotension, myocardial infarction, palpitations, peripheral edema, shock (circulatory failure), sinus tachycardia, syncope, and vasodilation. In addition, the following laboratory parameter alterations were also reported as adverse events during clinical evaluation of oral lansoprazole: hyperlipidemia, increased/decreased cholesterol, and increased LDH.
In lansoprazole clinical trials, diarrhea was one of the most frequently reported adverse reactions (oral: 1.4% to 7.4%; IV: less than 1%) and appears to be dose-related. In patients being treated for H.pylori, diarrhea (7%) was reported among patients receiving lansoprazole plus amoxicillin and clarithromycin triple therapy; diarrhea (8%) was also reported for patients receiving lansoprazole and amoxicillin dual therapy. Although transient diarrhea associated with PPI therapy is typically mild and not troublesome, persistent watery diarrhea may require medical attention. In a prospective multi-center study of 186 pediatric patients (aged 4 to 36 months) that compared infants and children receiving gastric acidity (GA) inhibitors to a healthy control, the use of GA-inhibitors was associated with an increased risk of developing acute gastroenteritis. The patients in the study were otherwise healthy infants and children that were receiving omeprazole for gastroesophageal reflux treatment. In a case-controlled study of 136 pediatric patients (68 patients with Clostridium difficile-associated diarrhea and 68 controls negative for Clostridium difficile-associated diarrhea), the use of proton pump inhibitors was significantly higher in the Clostridium difficile positive group compared with the Clostridium difficile negative group (odds ratio (OR) = 4.5; 95% confidence interval (CI) = 1.4 to 14.4). In February 2012, the FDA notified the public of a possible association between gastric acid suppression drugs, such as proton pump inhibitors (PPI), and the development of Clostridium difficile-associated diarrhea (CDAD); suppression from histamine H2 receptor blocker administration is also under review. Gastric acid suppression has been proposed as an independent risk factor for the development of CDAD, particularly with PPIs; however, studies have shown conflicting results. Consideration should be given to the diagnosis of CDAD and pseudomembranous colitis in patients presenting with watery diarrhea, abdominal pain, and fever that does not improve following gastric acid suppression therapy and/or antibacterial administration. If diarrhea develops during therapy, the drug should be discontinued. Following diagnosis of pseudomembranous colitis, therapeutic measures should be instituted. Products inhibiting peristalsis are contraindicated in this clinical situation. Practitioners should be aware that antibiotic-associated colitis has been observed to occur over 2 months or more following discontinuation of systemic antibiotic therapy; a careful medical history should be taken. Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program. In general, patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.
Chronic use of gastric acid-suppressing agents should be used cautiously and with monitoring in patients who are prone to vitamin B12 deficiency. Daily treatment with a gastric acid-suppressing medication, such as lansoprazole, over a long period of time (e.g., generally >= 2-3 years) has been associated with malabsorption of cyanocobalamin in adults. Consider the possibility of cyanocobalamin deficiency if clinical symptoms are observed.
Lansoprazole elimination half-life is significantly prolonged in patients with hepatic disease. In patients with severe hepatic disease, dosage reduction of lansoprazole should be considered. Abnormal liver-function tests have been reported infrequently with lansoprazole use.
The use of proton pump inhibitors (PPIs) may be associated with an increased risk of Clostridium difficile-associated diarrhea (CDAD), especially in hospital patients. 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 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). The PPIs, including lansoprazole, 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.
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 lansoprazole does not preclude the presence of gastric cancer or other malignancy.
Patients with phenylketonuria should be made aware that lansoprazole disintegrating tablets contain phenylalanine (2.5 mg per 15 mg tablet; 5.1 mg per 30 mg tablet). The capsule formulation does not contain phenylalanine.
Use lansoprazole with caution in pediatric patients with low bone density. Observational studies have suggested that proton pump inhibitors (PPIs) may be associated with an increased risk for osteoporosis related fractures of the hip, wrist, or spine. In studies, patients at highest risk of fracture were those who received high-dose (defined as multiple daily doses) and long-term PPI therapy (a year or longer). Until more data are available, 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 osteoporosis, manage their bone status according to current clinical practice, and ensure adequate vitamin D and calcium supplementation.
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 lansoprazole. 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.
Lansoprazole is contraindicated in patients who have shown lansoprazole hypersensitivity. Lansoprazole 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 or angioedema). Acute tubulo-interstitial nephritis (TIN or AIN) has been observed in patients taking PPIs and 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). There have been reports of patients who were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue lansoprazole and evaluate patients with suspected acute TIN.
Use with caution in patients with a history of systemic lupus erythematosus (SLE) as lansoprazole has been reported to activate or exacerbate SLE.
Administration of lansoprazole may result in laboratory test interference, specifically serum chromogranin A (CgA) tests for neuroendocrine tumors, urine tests for tetrahydrocannabinol (THC), secretin stimulation tests, and diagnostic tests for Helicobacter pylori. Gastric acid suppression may increase serum CgA. Increased CgA concentrations may cause false positive results in diagnostic investigations for neuroendocrine tumors. To prevent this interference, temporarily stop lansoprazole at least 14 days before assessing CgA concentrations and consider repeating the test if initial concentrations are high. If serial tests are performed, ensure the same commercial laboratory is used as reference ranges may vary. Reports have suggested use of proton pump inhibitors (PPIs) may cause false positive urine screening tests for THC. If a PPI-induced false positive urine screen is suspected, confirm the positive results using an alternative testing method. PPIs may also cause a hyper-response in gastrin secretion to the secretin stimulation test, falsely suggesting gastrinoma. Health care providers are advised to temporarily stop lansoprazole at least 28 days prior to performing a secretin stimulation test to allow gastrin concentrations to return to baseline. Preparations that combine PPIs with antimicrobials and bismuth are known to suppress H. pylori; thus, ingestion of these preparations within 4 weeks of performing diagnostic tests for H. pylori may lead to false negative results. At a minimum, instruct the patient to avoid the use of lansoprazole in the 1 to 2 weeks prior to the test and the use of antimicrobials and bismuth preparations in the 4 weeks prior to the test.
The safety and efficacy of lansoprazole have not been established in neonates or infants; however, the drug has been used off-label with caution in these populations. A multicenter, double-blind, placebo-controlled study including infants (1 month to younger than 1 year of age) with symptomatic GERD failed to show safety and efficacy. Limited data are available describing lansoprazole use in neonates. In nonclinical studies in juvenile rats, heart valve thickening and bone changes (delayed growth and impairment of weight gain) were reported at doses at least 2.5 times higher than the maximum recommended equivalent human dose. Patients 1 year of age and older do not appear to be at risk of heart valve injury.
Description: Lansoprazole is an acid proton-pump inhibitor (PPI). It is used for the short-term treatment of duodenal or gastric ulcers, gastroesophageal reflux disease (GERD), erosive esophagitis, and for long-term treatment of Zollinger-Ellison syndrome (pathological hypersecretory condition). It is also indicated to maintain healing of duodenal ulcer and esophagitis, for NSAID-induced ulcer treatment or prophylaxis, and for use in combination with antibiotics in the eradication of Helicobacter pylori (H. pylori) to reduce the risk of duodenal ulcer recurrence. Although many studies have demonstrated some benefit from the use of PPIs in the treatment of GERD or erosive esophagitis when compared to placebo, conflicting evidence on the safety and efficacy of PPIs warrants cautious use of these drugs in pediatric patients, particularly infants. PPIs are not recommended as first-line therapy for symptomatic GERD in otherwise healthy infants (1 to 11 months); nonpharmacologic measures such as diet modification and positioning strategies are recommended first-line and treatment with PPIs should be reserved for use in infants with acid reflux disease diagnosed by endoscopy (e.g., erosive esophagitis). Clinically, lansoprazole is at least as effective as omeprazole in treating peptic ulcers and reflux esophagitis, and it has been shown to relieve reflux symptoms more quickly than either omeprazole or ranitidine in adult patients. Over a 4-week period, ulcer healing was greater with lansoprazole than ranitidine or placebo in a double-blind study of the treatment of active duodenal ulcer. A comparative study of omeprazole and lansoprazole in the short-term treatment of reflux esophagitis showed no significant difference in healing after 4 or 8 weeks. Lansoprazole, however, showed greater improvement in heartburn and acid regurgitation symptoms after 4 weeks. On the basis of available research, no clear advantage has been demonstrated for the use of 1 PPI over another in the treatment of GERD. Instead, a key to optimizing effectiveness is tailoring dosage timing; administer traditional delayed-release PPIs 30 to 60 minutes before a meal for maximal pH control. A one-time switch to a different PPI in a refractory patient may be useful. A non-prescription (OTC) lansoprazole product (Prevacid 24HR) is available in its prescription-strength formula for the treatment of frequent heartburn. PPIs have been associated with an increased risk of Clostridium difficile-associated diarrhea. In a retrospective case-controlled trial in 136 pediatric patients, the use of PPI was significantly higher in the Clostridium difficile positive group compared with the Clostridium difficile negative group (OR = 4.5; 95% CI = 1.4 to 14.4). Lansoprazole is FDA-approved in pediatric patients as young as 1 year of age.
For the short-term treatment and maintenance of symptomatic gastroesophageal reflux disease (GERD) and erosive esophagitis:
Neonates*: Limited data are available describing use in neonates; dosing has not been established. A dose of 0.2-0.3 mg/kg/day PO given 30 minutes before a meal for 4 weeks was used in patients <= 10 weeks in a randomized, placebo controlled trial (n = 52); however, no difference in symptoms was noted between lansoprazole and placebo. Larger doses of 0.5-1.5 mg/kg/day PO given in 1 or 2 doses per day have been used in smaller, short-term case series (n = 10-24). In one study, 10 premature neonates (mean weight = 1.27 kg, mean postnatal age = 2 weeks) received lansoprazole 1.5 mg/kg/day PO divided into 2 doses. After 7 days of treatment, gastric pH increased but not above 2 in any patient. Based on pharmacokinetic data from 24 neonates and infants, it appears that infants <= 10 weeks of age achieve similar drug exposure after smaller doses compared to infants > 10 weeks of age due to slower clearance.
Infants <= 10 weeks*: Limited data are available describing use in infants < = 10 weeks of age. A dose of 0.2-0.3 mg/kg/day PO given 30 minutes before a meal for 4 weeks was used in patients <= 10 weeks in a randomized, placebo controlled trial (n = 52); however, no difference in symptoms was noted between lansoprazole and placebo. Doses up to 2 mg/kg/day PO have been reported. Pharmacokinetic data suggest that infants <= 10 weeks of age achieve similar drug exposure after smaller doses compared to infants > 10 weeks of age due to slower clearance. In a phase I trial, 24 infants (> 4 weeks) received lansoprazole 1 or 2 mg/kg/day PO for 5 days. It was well tolerated and a decrease in the frequency of gastroesophageal reflux symptoms was observed. PPIs are not recommended as first-line therapy for symptomatic GERD in otherwise healthy infants (1-11 months); nonpharmacologic measures such as diet modification and positioning strategies are recommended. Reserve pharmacologic treatment for use in infants with disease diagnosed by endoscopy (e.g., esophageal erosion).
Infants > 10 weeks*: Limited data are available describing use in infants > 10 weeks of age; an initial dose of 1-2 mg/kg/day PO given 30 minutes before a meal has been studied. In a phase I trial, 24 infants received lansoprazole 1 or 2 mg/kg/day for 5 days. It was well tolerated and a decrease in the frequency of gastroesophageal reflux symptoms was observed. In a retrospective analysis, the medical charts of 158 infants who received lansoprazole were reviewed. The median lansoprazole dose was 1.74 mg/kg/day PO. This study did not evaluate clinical outcomes or safety. In a double-blind, placebo-controlled trial of 162 infants (aged 1-12 months), lansoprazole was not found to be effective as defined by a > 50% reduction in either the percent of feedings with a crying/fussing/irritability episode or the duration of a crying/fussing/irritability episode within 1 hour of feeding. Infants received lansoprazole suspension 1-1.5 mg/kg/day PO. A study of 30 infants (aged 3-7 months) compared 15 mg/day given once daily PO to 7.5 mg/dose given twice daily. The twice-daily regimen produced faster symptom response, but both regimens produced significant improvement in symptoms, compared to the control group. PPIs are not recommended as first-line therapy for symptomatic GERD in otherwise healthy infants (1-11 months); nonpharmacologic measures such as diet modification and positioning strategies are recommended. Reserve pharmacologic treatment for use in infants with disease diagnosed by endoscopy (e.g., esophageal erosion).
Children 1-11 years and <= 30 kg: 15 mg PO once daily in the morning at least 30 minutes before a meal for up to 12 weeks. Alternatively, a dose range of 0.7-3 mg/kg/day PO is recommended by the American Academy of Pediatrics (AAP). Initial doses of 1.4-1.5 mg/kg/day PO have also been suggested in medical literature.
Children <= 11 years and >= 30 kg: 30 mg PO once daily in the morning at least 30 minutes before a meal for up to 12 weeks. Initial doses of 1.4-1.5 mg/kg/day PO have been reported in medical literature. The dosage was increased (Max: 30 mg PO twice daily) in some children who were symptomatic after 2 weeks in some trials ; however, the usual maximum adult dosage for most indications is 30 mg/day.
Children >= 12 years and Adolescents: 15 mg PO once daily in the morning at least 30 minutes before a meal, for up to 8 weeks. If the patient has symptomatic erosive or recurrent GERD, initially 30 mg PO once daily in the morning at least 30 minutes before a meal for up to 8 weeks. If healing is incomplete or recurs, a further 8 weeks of therapy can be considered. For the maintenance of healing of erosive esophagitis, 15 mg PO once daily in the morning at least 30 minutes before a meal should be administered. Controlled studies do not extend beyond 12 months. In one clinical study, 173 patients were randomized to placebo, lansoprazole 15 mg, or lansoprazole 30 mg PO once daily before breakfast for 12 months. Lansoprazole was superior to placebo, although there was no difference between the 2 doses.
For Helicobacter pylori (H. pylori) eradication*:
-in combination with amoxicillin and clarithromycin:
Children and Adolescents: 1.5 to 2.5 mg/kg/day PO divided twice daily (Max: 30 mg/dose) in combination with amoxicillin and clarithromycin for 14 days. Triple therapy with standard-dose amoxicillin, clarithromycin, and a proton pump inhibitor is a first-line treatment option for patients infected with fully susceptible H. pylori strains or strains susceptible to clarithromycin but resistant to metronidazole. In cases of penicillin allergy, use metronidazole in place of amoxicillin for patients infected with fully susceptible strains.
-in combination with amoxicillin and metronidazole:
Children and Adolescents: 1.5 to 2.5 mg/kg/day PO divided twice daily (Max: 30 mg/dose) in combination with amoxicillin and metronidazole for 14 days. Triple therapy with standard-dose amoxicillin, metronidazole, and a proton pump inhibitor (PPI) is a first-line treatment option for patients infected with H. pylori strains with known susceptibility to metronidazole and resistance to clarithromycin. Triple therapy with high-dose amoxicillin, metronidazole, and a PPI is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility.
-as part of a sequential therapy regimen:
Children and Adolescents: 1.5 to 2.5 mg/kg/day PO divided twice daily (Max: 30 mg/dose) for 10 days. Use in combination with amoxicillin for days 1 through 5, and then clarithromycin and metronidazole for days 6 through 10. Sequential therapy is a first-line treatment option for patients infected with fully susceptible H. pylori strains. Sequential therapy is not recommended if susceptibility testing is unavailable.
-as part of a quadruple therapy regimen:
Children and Adolescents: 1.5 to 2.5 mg/kg/day PO divided twice daily (Max: 30 mg/dose) in combination with amoxicillin, metronidazole, and clarithromycin for 14 days. Concomitant quadruple therapy with amoxicillin, metronidazole, clarithromycin, and a proton pump inhibitor is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility.
Maximum Dosage Limits:
Safety and efficacy have not been established; doses up to 1.5 mg/kg/day have been used off-label for GERD.
Safety and efficacy have not been established; doses up to 2 mg/kg/day PO have been used off-label for GERD.
1 to 11 years weighing 30 kg or less: 15 mg/day PO for GERD or erosive esophagitis, occasionally higher doses used for refractory cases; up to 2.5 mg/kg/day PO (Max: 60 mg/day) has been used off-label for eradication of H. pylori.
1 to 11 years weighing more than 30 kg: 30 mg/day PO for GERD or erosive esophagitis, up to 60 mg/day PO has been used off-label for refractory cases and for eradication of H. pylori.
12 years: 30 mg/day PO for most indications; up to 60 mg/day PO has been used off-label for eradication of H. pylori.
30 mg/day PO for most indications; up to 60 mg/day PO has been used off-label for eradication of H. pylori.
Patients with Hepatic Impairment Dosing
Consider dosage reduction in patients with severe hepatic disease; specific recommendations are not available. In patients with chronic hepatic impairment, an increase in the mean AUC of up to 500% was observed at steady state compared to healthy subjects.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Lansoprazole is not removed by hemodialysis.
Monograph content under development
Mechanism of Action: Lansoprazole belongs to the class of GI antisecretory agents, the substituted benzimidazoles, that suppress gastric acid secretion by inhibiting the (H+, K+)-ATPase enzyme system of parietal cells. An acidic environment in the parietal cell is required for conversion of gastric-acid pump inhibitors, such as lansoprazole, to the active sulfenamide metabolite. The active metabolite then inhibits the ATPase enzyme required for gastric-acid pump activation, thereby 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 of lansoprazole. In hypersecretory conditions, lansoprazole has a marked effect on gastric acid secretion, both basal- and pentagastrin-stimulated. Lansoprazole exerts an inhibitory effect on gastric acid for at least 24 hours, which allows a once-daily dosing schedule. Lansoprazole does not antagonize H2 or cholinergic receptors. Lansoprazole induced increases in mucosal oxygenation or bicarbonate secretion may play a role in protecting the gastric mucosa from injury.
Acid suppression may enhance the effect of antimicrobials in eradicating Helicobacter pylori (H. pylori).
Pharmacokinetics: Lansoprazole is administered orally and intravenously. Lansoprazole is about 97% bound to plasma protein. Lansoprazole is believed to be transformed into 2 active inhibitors of acid secretion in the gastric parietal cells. Serum gastrin levels increase 50% to 100% from baseline in the fasting state, and these increases are greater during lansoprazole therapy than during ranitidine therapy. Increases reach a plateau within 2 months and return to pretreatment levels within 4 weeks of discontinuation of lansoprazole therapy. Hepatic metabolism of lansoprazole is extensive. The 2 identified hepatic metabolites of lansoprazole have little antisecretory activity. Plasma elimination half-life, which is less than 2 hours, is not related to gastric antisecretory effect, which lasts more than 24 hours. Elimination is believed to occur via biliary excretion. Almost no unchanged lansoprazole is detected in urine after single-dose administration. After administration of a single dose of radio-labeled lansoprazole, one-third of the administered radiation was excreted in urine and two-thirds in the feces.
Affected cytochrome P450 isoenzymes: CYP3A4, CYP2C19
Lansoprazole is a substrate of the cytochrome P450 system via the CYP2C19 and CYP3A4 isoenzymes.
All lansoprazole oral dosage forms (capsules, oral suspension, and disintegrating tablets) contain delayed-release, enteric-coated granules that release drug after they leave the stomach. Absorption of lansoprazole is rapid; mean peak plasma concentrations occur after about 1.7 hours. The absolute bioavailability is over 80%, which can be reduced by 50% to 70% if lansoprazole is given 30 minutes after food. The time to reach Cmax is also delayed by 3.5 to 3.7 hours when administered with food. Antacids can also affect absorption and can cause a slight reduction in bioavailability.
After the administration of 30 mg of lansoprazole by intravenous infusion over 30 minutes to healthy adults, plasma concentrations of lansoprazole declined exponentially with a mean terminal elimination half-life of 1.3 hours. The mean Cmax was 1705 ng/ml and the mean AUC was 3192 ng x h/ml.
Neonates and Infants
The plasma exposure is higher and the elimination is lower after administration of oral lansoprazole to neonates and infants 10 weeks of age or younger compared to older pediatric patients and adults. In a pharmacokinetic study of neonates and infants with gastroesophageal reflux disease, neonates received doses of 0.5 to 1 mg/kg/day PO and infants received 1 to 2 mg/kg/day PO for 5 days. The half-life was increased (2 to 2.8 hours vs. 0.8 hours) and oral clearance was decreased (0.16 L/h/kg vs. 0.61 to 0.71 L/h/kg) in neonates, compared to infants. A post hoc examination of the data showed that infants 10 weeks or younger had Cmax and AUC values more than 2 and 5 times higher, respectively, than those in infants older than 10 weeks to 1 year. The mean half-life of lansoprazole was approximately 3 times greater in pediatric patients 10 weeks and younger compared to patients older than 10 weeks (2.3 hours vs. 0.8 hours). In another pharmacokinetic study of neonates, infants, and children with gastroesophageal reflux disease, doses of 0.5 and 1 mg/kg/day PO given to neonates and infants 10 weeks of age or younger resulted in higher mean weight-based normalized AUC values compared to adults who received a 30 mg dose. In infants at least 10 weeks of age, a dose of 1 mg/kg PO resulted in mean AUC values similar to that of adults who received a dose of 30 mg.
The pharmacokinetics of lansoprazole are similar for children older than 1 year of age, adolescents, and healthy adult subjects. The mean Cmax and AUC values are similar for two weight-adjusted dosage groups: 15 mg/day for weight 30 kg or less and 30 mg/day for weight more than 30 kg; pharmacokinetics are not affected by age or weight within these groups. The mean volume of distribution of lansoprazole in children is larger than reported in adults (0.6 to 0.9 L/kg vs. 0.39 to 0.46 L/kg). The mean elimination half-life ranges from 0.68 to 1.5 hours in children aged 1 to 11 years.
Lansoprazole: Lansoprazole serum concentrations are increased in patients with hepatic disease. In patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment, there was an approximate 3-fold increase in mean AUC compared to normal subjects. The corresponding mean plasma half-life was prolonged from 1.5 to 4 hours (Child-Pugh Class A) or 5 hours (Child-Pugh Class B). In patients with compensated and decompensated cirrhosis, there was an approximated 6- and 5-fold increase in AUC, respectively, compared to health subjects.
Lansoprazole serum concentrations are not affected by renal dysfunction or hemodialysis. Pharmacokinetic parameters are not changed by the presence of renal impairment. Lansoprazole is not removed by hemodialysis.