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 oral lansoprazole trials compared to placebo (2.1% vs 1.2%) and less frequently (less than 1%) in IV lansoprazole trials. Nausea was reported in 1.3% of patients receiving lansoprazole compared to 1.2% receiving placebo. 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. 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 stomatitis, vomiting, and xerostomia. Gastric polyps/fundic gland polyps have been reported during postmarketing surveillance.[28954] [40596]

During lansoprazole clinical evaluation, headache was reported in more than 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. In pediatric patients, headache was reported in 3% of patients aged 1 to 11 year and in 7% of patients aged 12 to 17 years. Other nervous system adverse reactions reported in less than 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, libido decrease, libido increase, migraine, nervousness, neurosis, paresthesias, parosmia, seizures, sleep disorder, thinking abnormality, tremor, vertigo, and visual field defect. During postmarketing surveillance, speech disorder was also reported.[28954] [40596]

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.[28954] [40596]

Hematological adverse reactions that have been reported in <1% of patients 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.[28954] [40596] Long-term (e.g., generally >= 2—3 years) treatment with acid-suppressing agents can lead to malabsorption of vitamin B12 (cyanocobalamin).[40596] [56553] In a study of healthy volunteers, it was shown that omeprazole caused a significant reduction in cyanocobalamin absorption (vitamin B12 deficiency).[23614] One large case-controlled study compared patients with and without an incident diagnosis of vitamin B12 deficiency (n = 25,956 and 184,199, respectively). A correlation was demonstrated between vitamin B12 deficiency and gastric acid-suppression therapy. Patients receiving >= 2 years of a proton pump inhibitor (PPI)(OR, 1.65 [95% CI, 1.58—1.73]) or >= 2 years of a H₂-receptor antagonist (OR, 1.25 [95% CI, 1.17—1.34]) were associated with having an increased risk for vitamin B12 deficiency. A dose-dependant relationship was evident, as daily doses > 1.5 PPI pills/d were more strongly associated with vitamin B12 deficiency (OR, 1.95 [95% CI, 1.77—2.15]) compared to daily doses < 0.75 pills/d (OR, 1.63 [95% CI, 1.48—1.78]; p = 0.007 for interaction).[56553] The possibility of cyanocobalamin deficiency and pernicious anemia should be considered if clinical symptoms are observed. Neurological manifestations of pernicious anemia can occur in the absence of hematologic changes.

During clinical evaluation, rash was reported in less than 1% of patients receiving oral lansoprazole and in 1% of patients receiving the IV formulation. Other dermatological reactions reported in less than 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 postmarketing surveillance include: anaphylactoid reactions, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). Discontinue lansoprazole and consider further evaluation if patient develops signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity.[28954] [40596]

During IV lansoprazole trials, injection site reaction including injection site pain was reported in 1% of patients.[28954]

Colitis and ulcerative colitis have been reported among events occurring in less than 1% of oral lansoprazole-treated patients during clinical trials.[40596] 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 patients treated with lansoprazole. One case series included six patients who developed microscopic colitis after a formulary switch to lansoprazole from omeprazole.[33152] 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.[33191] 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. In addition, increasing evidence suggests a link between acid-suppression therapy and infection with 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.[32661] 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.[35601] Regardless of the mechanism, the use of H₂-blockers [32661] and/or PPIs [35601] has been associated with the development of pneumonia. Data from a large epidemiological trial, including 364,683 individuals who developed 5551 first occurrences of community-acquired pneumonia (CAP), suggest an increased risk of developing CAP among users of acid-suppressive therapy compared to those who stopped therapy. After adjusting for confounders, the adjusted relative risk (RR) for CAP among PPI users compared to those who stopped therapy was 1.89 (95% CI, 1.36—2.62). Likewise, users of H₂-blockers had an adjusted RR of 1.63 (95% CI, 1.07—2.48) compared to those who stopped therapy.[32661] In a second large cohort trial, including 63,878 hospital admissions, acid-suppressive therapy was ordered in 52% (83% PPI and 23% H₂- blocker, with some patients exposed to both) of new admissions. Hospital-acquired pneumonia occurred in 2,219 admissions (3.5%) with a higher incidence recorded among acid-suppressive therapy exposed patients compared to non-exposed patients. A subset analysis found a statistically significant association between PPI use (OR, 1.3; 95% CI, 1.1—1.4) and pneumonia. A non-significant association was found with H₂-blockers (OR, 1.2; 95% CI, 0.98—1.4); however, the lack of significance was attributed to the studies lack of power to detect significance for an OR of less than 1.3.[35601] 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.

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.[28954] [40596] Other renal and genitourinary (GU) reactions have been reported with PPI use. The following have been reported in less than 1% of patients during lansoprazole clinical trials: dysmenorrhea, dysuria, impotence (erectile dysfunction), increased urinary frequency, kidney calculus (nephrolithiasis), kidney pain, leukorrhea, menorrhagia, menstrual irregularity, pelvic pain, penis disorder, polyuria, testis disorder, urethral pain, urinary retention, urinary tract infection, urinary urgency, and urination impaired. 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. Urinary retention has been reported during postmarketing experience. In a study where patients took either a COX-2 inhibitor or naproxen and lansoprazole, renal impairment has been reported.[28954] [40596]

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.[28954] [40596] [60451]

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.[28954] [40596] 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.[40635][40636][40637][40639][40640][40641] 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[40636] and another study found an increase after 5–7 years of PPI use.[40637] Increased risk was primarily observed in patients >= 50 years old, patients taking prescription PPIs for at least one year, and patients who had been taking high doses (doses greater than those recommended with OTC 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.[40638] 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.

Hypomagnesemia, hypocalcemia, hypokalemia, and hyponatremia have been reported during postmarketing lansoprazole use. Cases of hypomagnesemia have been reported in association with prolonged (3 months to more than 1 year) proton pump inhibitor (PPI) use. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in patients at risk. Low serum magnesium may lead to serious adverse reactions such as muscle spasm (tetany), seizures, and irregular heartbeat (arrhythmias). Consider monitoring electrolyte concentrations and supplementing electrolytes when needed. Discontinuation of PPI therapy may be necessary.[43594] [40596]

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.[28954] [40596]

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.[28954] [40596]

C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with lansoprazole. PPI therapy, such as lansoprazole, may be associated with an increased risk of CDAD, especially in hospitalized patients. The use of gastric acid suppressive therapy, such as PPIs, may increase the risk of enteric infection or superinfection by encouraging the growth of gut microflora. If pseudomembranous colitis is suspected or confirmed, institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Vaginitis was reported in less than 1% of patients during clinical trials.[40596] [48664] [53446] [55326]

Lansoprazole is contraindicated in patients who have shown lansoprazole hypersensitivity. Lansoprazole is a proton pump inhibitor (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, and some cases have been serious (e.g., angioedema or anaphylaxis). Serious rash and severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), erythema multiforme, and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs. Discontinue the PPI at the first signs or symptoms of severe cutaneous adverse reactions or other hypersensitivity and consider further evaluation. Acute tubulo-interstitial nephritis (TIN) 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.[28954] [40596] [60451]

Daily treatment with gastric acid-suppressing medication such as lansoprazole over a long period of time (e.g., generally >= 2—3 years) may lead to malabsorption of cyanocobalamin and vitamin B12 deficiency.[40596] [56553] Cases of cyanocobalamin deficiency occurring with acid-suppression therapy have been reported in the literature.[23614] 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.[56553] The possibility of cyanocobalamin deficiency should, therefore, be considered if clinical symptoms are observed.[40596]

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.[40596]

Consider pseudomembranous colitis in patients presenting with diarrhea after PPI use. PPI therapy, such as lansoprazole, may be associated with an increased risk of C. difficile-associated diarrhea (CDAD), especially in hospitalized patients. CDAD may range in severity from mild to life-threatening. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.[40596] [48664] [53446] [55326]

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.[40596]

Use proton pump inhibitors (PPIs) in patients with or who have risk factors for osteoporosis 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.[40635] [40636] [40637] [40639] [40640] [40641] 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.[40596] 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.

Use lansoprazole with caution in patients with a pre-existing risk of hypocalcemia (e.g., hypoparathyroidism), hypokalemia, or hypomagnesemia; consider monitoring magnesium and calcium concentrations prior to initiating therapy and periodically while on treatment in these patients. Supplement with magnesium and/or calcium as needed and consider discontinuing proton pump inhibitor (PPI) therapy if hypomagnesemia or hypocalcemia is refractory to treatment. For patients expected to be on PPI therapy for a prolonged period of time or who take concomitant medications such as digoxin or those that may cause hypomagnesemia (e.g., diuretics), consider monitoring of serum magnesium prior to initiation and periodically during treatment. Daily treatment with a PPI over a long period of time (e.g., 3 months to more than 1 year) may lead to hypomagnesemia; cases have been reported in patients taking lansoprazole. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in patients at risk. In most patients, the treatment of hypomagnesemia required magnesium replacement and PPI discontinuation. Low serum magnesium may lead to serious adverse reactions such as muscle spasm (tetany), seizures, and irregular heartbeat (arrhythmias).[40596] Use PPIs with caution and, if possible, avoid long-term (greater than 14 days) use in patients with congenital long QT syndrome, as they may be at higher risk for arrhythmias.[28225]

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.[57393] In this hypersecretory state, enterochromaffin-like cell hypertrophy also results in a temporal increase in serum chromogranin A (CgA) levels.[29564] 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.[57394] 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.[57394] [57395] [57396] [57397] 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.[55326]

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. No adverse effects on embryo-fetal development occurred in animal 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) during organogenesis and pregnant rabbits at oral lansoprazole doses up to 30 mg/kg/day (16 times the recommended human dose based on body surface area) during organogenesis. A pre- and postnatal developmental toxicity study in rats during organogenesis through lactation at 6.4 times the maximum recommended human dose produced reductions in the offspring in femur weight, femur length, crown-rump length and growth plate thickness (males only) on postnatal Day 21; these effects were associated with reduction in body weight gain. In a prospective study, outcomes from pregnant women (n= 62) administered lansoprazole (30 mg/day median dose) were compared to a pregnant control group (n=868) who did not take any proton pump inhibitors (PPIs). There was no difference in the rate of major malformations between women exposed to PPIs and the control group, (RR = 1.04, 95% CI 0.25 to 4.21). In a retrospective cohort study covering all live births in Denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of first trimester exposure to lansoprazole in 794 live births.[40596] In a meta-analysis that compared 1,530 pregnant women exposed to PPIs in at least the first trimester with 133,410 unexposed pregnant women, there were no significant increases in risk for congenital malformations or spontaneous abortion with exposure to PPIs for major malformations (OR =1.12, 95% CI 0.86 to 1.45) and for spontaneous abortions (OR = 1.29, 95% CI 0.84 to 1.97).[40596] [68893] Guidelines recommend a trial of lifestyle modifications as first-line therapy for heartburn and gastroesophageal reflux disease (GERD) during pregnancy, followed by antacids if lifestyle adjustments are ineffective. For ongoing symptoms, histamine type 2-receptor antagonists (H2RAs) can be used. Proton pump inhibitors should be reserved for pregnant patients who fail H2RA therapy.[68890] Self-medication with proton pump inhibitors (OTC formulations) during pregnancy is not recommended. Pregnant patients should see their health care professional for a proper diagnosis and for treatment recommendations.[45899] [68890]

Lansoprazole and its metabolites are present in rat milk. The clinical effects of proton pump inhibitor (PPI) exposure on the breastfed infant or on milk production have not been confirmed and PPI use is not recommended while breast-feeding; consider the developmental and health benefits of breast-feeding along with the clinical need for lansoprazole and any potential adverse effects on the breastfed infant or from the underlying maternal condition.[40596] [68890] According to guidelines, if heartburn/gastroesophageal reflux (GERD) symptoms persist after delivery, antacids and sucralfate are safe to use because they are not concentrated in breast milk. Histamine type 2-receptor antagonists (H2RAs) are excreted in breast milk, but cimetidine and famotidine are considered safe for use during lactation and may be used if symptoms persist despite antacid use.[45899] [68890]

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 and syrup formulations do not contain phenylalanine.

The safety and efficacy of lansoprazole has 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 one year of age and older do not appear to be at risk of heart valve injury.[40596] [53284] [53435] [53443]

Use with caution in patients with a history of systemic lupus erythematosus (SLE) as lansoprazole has been reported to activate or exacerbate SLE.[28954] [40596] [60451]

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.[40596] 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.[63135] [63136]

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]