Lansoprazole Drug Information

Recommended Adult Dosage by

Please refer to the amoxicillin and clarithromycin full prescribing information CONTRAINDICATIONS and WARNINGS and PRECAUTIONS sections, and for information regarding dosing in elderly and renally-impaired patients. Controlled studies did not extend beyond indicated duration. For patients who do not heal with lansoprazole for eight weeks (5 to 10%), it may be helpful to give an additional eight weeks of treatment. If there is a recurrence of erosive esophagitis, an additional eight week course of lansoprazole may be considered. ¶ Varies with individual patient. Recommended adult starting dose is 60 mg once daily.

Doses should be adjusted to individual patient needs and should continue for as long as clinically indicated. Dosages up to 90 mg twice daily have been administered. Daily dose of greater than 120 mg should be administered in divided doses.

It is not known if Lansoprazole delayed-release capsules are safe and effective if used longer than the recommended duration. Do not exceed the recommended dose and duration of use in pediatric patients as outlined below. Do not crush or chew Lansoprazole delayed-release capsules Take Lansoprazole delayed-release capsules at least 30 minutes prior to sucralfate.

Antacids may be used concomitantly with Lansoprazole delayed-release capsules. Missed doses: If a dose is missed, administer as soon as possible. However, if the next scheduled dose is due, do not take the missed dose, and take the next dose on time.

Do not take two doses at one time to make up for a missed dose. Lansoprazole Delayed-Release Capsules Swallow whole; do not chew. For patients who have difficulty swallowing capsules, Lansoprazole delayed-release capsules can be opened and administered orally or via a nasogastric tube in the soft foods or liquids specified below.

Administration of Lansoprazole delayed-release capsules in foods or liquids other than those discussed below have not been studied clinically and therefore are not recommended. Administration in Soft Foods (applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears): 1.Open capsule. 2.Sprinkle intact granules on one tablespoon of either applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears. 3.Swallow immediately. Administration in Liquids (apple juice, orange juice or tomato juice): 1.Open capsule. 2.Sprinkle intact granules into a small volume of either apple juice, orange juice or tomato juice (60 mL – approximately two ounces). 3.Mix briefly. 4.Swallow immediately. 5.To ensure complete delivery of the dose, rinse the glass with two or more volumes of juice and swallow the contents immediately.

Administration with Apple Juice Through a Nasogastric Tube (≥16 French) 1.Open capsule. 2.Sprinkle intact granules into 40 mL of apple juice. 3.Mix briefly 4.Using a catheter tipped syringe, draw up the mixture 5.Inject through the nasogastric tube into the stomach. 6.Flush with additional apple juice to clear the tube.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Worldwide, over 10,000 patients have been treated with lansoprazole in Phase 2 or Phase 3 clinical trials involving various dosages and durations of treatment. In general, lansoprazole treatment has been well-tolerated in both short-term and long-term trials.

The following adverse reactions were reported by the treating physician to have a possible or probable relationship to drug in 1% or more of lansoprazole delayed-release capsule-treated patients and occurred at a greater rate in lansoprazole delayed-release capsule-treated patients than placebo-treated patients in Table 1. Table 1. Incidence of Possibly or Probably Treatment-Related Adverse Reactions in Short-Term, Placebo-Controlled Lansoprazole Studies Headache was also seen at greater than 1% incidence but was more common on placebo.

The incidence of diarrhea was similar between patients who received placebo and patients who received 15 mg and 30 mg of lansoprazole, but higher in the patients who received 60 mg of lansoprazole respectively. The most commonly reported possibly or probably treatment-related adverse event during maintenance therapy was diarrhea. In the risk reduction study of lansoprazole for NSAID-associated gastric ulcers, the incidence of diarrhea for patients treated with lansoprazole, misoprostol, and placebo was 5%, 22%, and 3%, respectively.

Another study for the same indication, where patients took either a COX-2 inhibitor or lansoprazole and naproxen, demonstrated that the safety profile was similar to the prior study. Additional reactions from this study not previously observed in other clinical trials with lansoprazole included contusion, duodenitis, epigastric discomfort, esophageal disorder, fatigue, hunger, hiatal hernia, hoarseness, impaired gastric emptying, metaplasia, and renal impairment. Additional adverse experiences occurring in less than 1% of patients or subjects who received lansoprazole in domestic trials are shown below: Body as a Whole – abdomen enlarged, allergic reaction, asthenia, back pain, candidiasis, carcinoma, chest pain (not otherwise specified), chills, edema, fever, flu syndrome, halitosis, infection (not otherwise specified), malaise, neck pain, neck rigidity, pain, pelvic pain Cardiovascular System – angina, arrhythmia, bradycardia, cerebrovascular accident/cerebral infarction, hypertension/hypotension, migraine, myocardial infarction, palpitations, shock (circulatory failure), syncope, tachycardia, vasodilation Digestive System – abnormal stools, anorexia, bezoar, cardiospasm, cholelithiasis, colitis, dry mouth, dyspepsia, dysphagia, enteritis, eructation, esophageal stenosis, esophageal ulcer, esophagitis, fecal discoloration, flatulence, gastric nodules/fundic gland polyps, gastritis, gastroenteritis, gastrointestinal anomaly, gastrointestinal disorder, gastrointestinal hemorrhage, glossitis, gum hemorrhage, hematemesis, increased appetite, increased salivation, melena, mouth ulceration, nausea and vomiting, nausea and vomiting and diarrhea, gastrointestinal moniliasis, rectal disorder, rectal hemorrhage, stomatitis, tenesmus, thirst, tongue disorder, ulcerative colitis, ulcerative stomatitis Endocrine System – diabetes mellitus, goiter, hypothyroidism Hemic and Lymphatic System – anemia, hemolysis, lymphadenopathy Metabolism and Nutritional Disorders – avitaminosis, gout, dehydration, hyperglycemia/hypoglycemia, peripheral edema, weight gain/loss Musculoskeletal System – arthralgia, arthritis, bone disorder, joint disorder, leg cramps, musculoskeletal pain, myalgia, myasthenia, ptosis, synovitis Nervous System – abnormal dreams, agitation, amnesia, anxiety, apathy, confusion, convulsion, dementia, depersonalization, depression, diplopia, dizziness, emotional lability, hallucinations, hemiplegia, hostility aggravated, hyperkinesia, hypertonia, hypesthesia, insomnia, libido decreased/increased, nervousness, neurosis, paresthesia, sleep disorder, somnolence, thinking abnormality, tremor, vertigo Respiratory System – asthma, bronchitis, cough increased, dyspnea, epistaxis, hemoptysis, hiccup, laryngeal neoplasia, lung fibrosis, pharyngitis, pleural disorder, pneumonia, respiratory disorder, upper respiratory inflammation/infection, rhinitis, sinusitis, stridor Skin and Appendages – acne, alopecia, contact dermatitis, dry skin, fixed eruption, hair disorder, maculopapular rash, nail disorder, pruritus, rash, skin carcinoma, skin disorder, sweating, urticaria Special Senses – abnormal vision, amblyopia, blepharitis, blurred vision, cataract, conjunctivitis, deafness, dry eyes, ear/eye disorder, eye pain, glaucoma, otitis media, parosmia, photophobia, retinal degeneration/disorder, taste loss, taste perversion, tinnitus, visual field defect Urogenital System – abnormal menses, breast enlargement, breast pain, breast tenderness, dysmenorrhea, dysuria, gynecomastia, impotence, kidney calculus, kidney pain, leukorrhea, menorrhagia, menstrual disorder, penis disorder, polyuria, testis disorder, urethral pain, urinary frequency, urinary retention, urinary tract infection, urinary urgency, urination impaired, vaginitis.

Postmarketing Experience

Additional adverse experiences have been reported since lansoprazole has been marketed. The majority of these cases are foreign-sourced and a relationship to lansoprazole has not been established. Because these reactions were reported voluntarily from a population of unknown size, estimates of frequency cannot be made.

These events are listed below by COSTART body system. Body as a Whole - anaphylactic/anaphylactoid reactions, systemic lupus erythematosus; Digestive System - hepatotoxicity, pancreatitis, vomiting; Hemic and Lymphatic System - agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic purpura; Infections and Infestations – Clostridium difficile associated diarrhea; Metabolism and Nutritional Disorders – hypomagnesemia, hypocalcemia, hypokalemia, hyponatremia; Musculoskeletal System - bone fracture, myositis; Skin and Appendages - severe dermatologic reactions including erythema multiforme, SJS/TEN (some fatal), DRESS, AGEP, cutaneous lupus erythematosus; Special Senses - speech disorder; Urogenital System - interstitial nephritis, urinary retention.

Combination Therapy with Amoxicillin and Clarithromycin

In clinical trials using combination therapy with lansoprazole plus amoxicillin and clarithromycin, and lansoprazole plus amoxicillin, no adverse reactions peculiar to these drug combinations were observed. Adverse reactions that have occurred have been limited to those that had been previously reported with lansoprazole, amoxicillin, or clarithromycin. There were no statistically significant differences in the frequency of reported adverse reactions between the 10- and 14-day triple therapy regimens.

No treatment-emergent adverse reactions were observed at significantly higher rates with triple therapy than with any dual therapy regimen. Dual Therapy: lansoprazole/amoxicillin The most frequently reported adverse reactions for patients who received lansoprazole three times daily plus amoxicillin three times daily dual therapy were diarrhea (8%) and headache (7%). No treatment-emergent adverse reactions were observed at significantly higher rates with lansoprazole three times daily plus amoxicillin three times daily dual therapy than with lansoprazole alone.

For information about adverse reactions with antibacterial agents (amoxicillin and clarithromycin) indicated in combination with lansoprazole, refer to the ADVERSE REACTIONS sections of their prescribing information.

Laboratory Values

The following changes in laboratory parameters in patients who received lansoprazole were reported as adverse reactions: Abnormal liver function tests, increased SGOT (AST), increased SGPT (ALT), increased creatinine, increased alkaline phosphatase, increased globulins, increased GGTP, increased/decreased/abnormal WBC, abnormal AG ratio, abnormal RBC, bilirubinemia, blood potassium increased, blood urea increased, crystal urine present, eosinophilia, hemoglobin decreased, hyperlipemia, increased/decreased electrolytes, increased/decreased cholesterol, increased glucocorticoids, increased LDH, increased/decreased/abnormal platelets, increased gastrin levels and positive fecal occult blood. Urine abnormalities such as albuminuria, glycosuria, and hematuria were also reported. Additional isolated laboratory abnormalities were reported.

In the placebo controlled studies, when SGOT (AST) and SGPT (ALT) were evaluated, patients, who received placebo and lansoprazole, respectively, had enzyme elevations greater than three times the upper limit of normal range at the final treatment visit. None of these patients who received lansoprazole reported jaundice at any time during the study. In clinical trials using combination therapy with lansoprazole plus amoxicillin and clarithromycin, and lansoprazole plus amoxicillin, no increased laboratory abnormalities particular to these drug combinations were observed.

Tables 2 and 3 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with lansoprazole delayed release capsules and instructions for preventing or managing them. Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs. Table 2.

Clinically Relevant Interactions Affecting Drugs Co-Administered with Lansoprazole Delayed Release Capsules and Interactions with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. Intervention: Rilpivirine-containing products: Concomitant use with Lansoprazole delayed release capsules is contraindicated. See prescribing information.

No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Temporarily stop Lansoprazole treatment at least 28 days before assessing to allow gastrin levels to return to baseline.

Table 3. Clinically Relevant Interactions Affecting Lansoprazole Delayed Release Capsules When CoAdministered with Other Drugs CYP2C19 OR CYP3A4 Inducers Clinical Impact: Decreased exposure of lansoprazole when used concomitantly with strong inducers Intervention: St John’s Wort, rifampin: Avoid concomitant use with Lansoprazole. CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of lansoprazole is expected when used concomitantly with strong inhibitors.

Intervention: Voriconazole: See prescribing information. Sucralfate Clinical Impact: Decreased and delayed absorption of lansoprazole. Intervention: Take Lansoprazole at least 30 minutes prior to sucralfate.

See full prescribing information for a list of clinically important drug interactions.

Pregnancy Risk Summary Available data from published observational studies overall do not indicate an association of adverse pregnancy outcomes with lansoprazole treatment (see Data). In animal reproduction studies, oral administration of lansoprazole to 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 (see Data). These effects were associated with reduction in body weight gain.

Advise pregnant women of the potential risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. If lansoprazole delayed release capsules are administered with clarithromycin, the pregnancy information for clarithromycin also applies to the combination regimen. Refer to the prescribing information for clarithromycin for more information on use in pregnancy.

Data Human Data 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. In a prospective study by the European Network of Teratology Information Services, outcomes from a group of 62 pregnant women administered median daily doses of 30 mg of lansoprazole were compared to a control group of 868 pregnant women who did not take any PPIs.

There was no difference in the rate of major malformations between women exposed to PPIs and the control group, corresponding to a Relative Risk (RR)=1.04,. In a population-based 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. A meta-analysis that compared 1,530 pregnant women exposed to PPIs in at least the first trimester with 133,410 unexposed pregnant women showed no significant increases in risk for congenital malformations or spontaneous abortion with exposure to PPIs (for major malformations Odds Ratio (OR)=1.12, and for spontaneous abortions OR=1.29, ).

Animal Data 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 based on body surface area) administered 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) administered during organogenesis. A pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with lansoprazole at oral doses of 10 to 100 mg/kg/day (0.7 to 6.4 times the maximum recommended human lansoprazole dose of 30 mg based on AUC ) administered during organogenesis through lactation. Maternal effects observed at 100 mg/kg/day (6.4 times the maximum recommended human lansoprazole dose of 30 mg based on AUC) included increased gestation period, decreased body weight gain during gestation, and decreased food consumption.

The number of stillbirths was increased at this dose, which may have been secondary to maternal toxicity. Body weight of pups was reduced at 100 mg/kg/day starting on postnatal Day 11. Femur weight, femur length, and crown-rump length were reduced at 100 mg/kg/day on postnatal Day 21.

Femur weight was still decreased in the 100 mg/kg/day group at age 17 to 18 weeks.

Pediatric Use The safety and effectiveness of Lansoprazole delayed-release capsules has been established in pediatric patients one year to 17 years of age for short-term treatment of symptomatic GERD and erosive esophagitis. In clinical studies of symptomatic GERD and erosive esophagitis, Lansoprazole delayed-release capsules were not administered beyond 12 weeks in patients one year to 11 years of age. It is not known if Lansoprazole delayed-release capsules are safe and effective if used longer than the recommended duration.

Do not exceed the recommended dose and duration of use in pediatric patients (see Juvenile Animal Toxicity Data). Lansoprazole delayed-release capsules were not effective in pediatric patients with symptomatic GERD one month to less than one year of age in a multicenter, double-blind, placebo-controlled study. Therefore, safety and effectiveness have not been established in patients less than one year of age.

Nonclinical studies in juvenile rats have demonstrated an adverse effect of heart valve thickening and bone changes at lansoprazole doses higher than the maximum recommended equivalent human dose. Neonate to less than one year of age The pharmacokinetics of lansoprazole were studied in pediatric patients with GERD aged less than 28 days and one month to 11 months. Infants aged ≤10 weeks had clearance and exposure values that were similar to neonates.

Infants aged greater than 10 weeks who received 1 mg/kg/day had mean AUC values that were similar to adults who received a 30 mg dose. Lansoprazole was not found to be effective in a U.S. and Polish four week multicenter, double-blind, placebo-controlled, parallel-group study of 162 patients between one month and less than 12 months of age with symptomatic GERD based on a medical history of crying/fussing/irritability associated with feedings who had not responded to conservative GERD management (i.e., non-pharmacologic intervention) for seven to 14 days. The primary efficacy endpoint was assessed by greater than 50% reduction from baseline in either the percent of feedings with a crying/fussing/irritability episode or the duration (minutes) of a crying/fussing/irritability episode within one hour after feeding.

There was no difference in the percentage of responders between the lansoprazole pediatric suspension group and placebo group (54% in both groups). There were no adverse events reported in pediatric clinical studies (one month to less than 12 months of age) that were not previously observed in adults. Based on the results of the Phase 3 efficacy study, lansoprazole was not shown to be effective.

Therefore, these results do not support the use of lansoprazole in treating symptomatic GERD in infants. The lansoprazole delayed-release capsules dose was increased (up to 30 mg twice daily) in 24 of 66 pediatric patients after two or more weeks of treatment if they remained symptomatic. At baseline 85% of patients had mild to moderate overall GERD symptoms (assessed by investigator interview), 58% had non-erosive GERD and 42% had erosive esophagitis (assessed by endoscopy).

After eight to 12 weeks of lansoprazole delayed-release capsules treatment, the intent-to-treat analysis demonstrated an approximate 50% reduction in frequency and severity of GERD symptoms. Table 4. In a study of 66 pediatric patients in the age group one year to 11 years old after treatment with lansoprazole given orally in doses of 15 mg daily to 30 mg twice daily, increases in serum gastrin levels were similar to those observed in adult studies.

Median fasting serum gastrin levels increased 89% from 51 pg/mL at baseline to 97 pg/mL at the final visit. The pediatric safety of lansoprazole delayed-release capsules has been assessed in 66 pediatric patients aged one year to 11 years of age. The most frequently reported (two or more patients) treatment-related adverse reactions in patients one year to 11 years of age (N=66) were constipation (5%) and headache (3%).

The nonerosive GERD patients received lansoprazole 15 mg daily for eight weeks and the EE patients received lansoprazole 30 mg daily for eight to 12 weeks. At baseline, 89% of these patients had mild to moderate overall GERD symptoms (assessed by investigator interviews). During 8 weeks of lansoprazole treatment, adolescent patients experienced a 63% reduction in frequency and a 69% reduction in severity of GERD symptoms based on diary results.

Twenty-one of 22 (95.5%) adolescent erosive esophagitis patients were healed after eight weeks of lansoprazole treatment. One patient remained unhealed after 12 weeks of treatment ( Table 5 ). Table 5.

GERD Symptom Improvement and Erosive Esophagitis Healing Rates in Pediatric Patients Age 12 Years to 17 Years of Age GERD Final Visit % (n/N) Symptomatic GERD (All Patients) Improvement in Overall GERD Symptoms* 73.2% (60/82) Nonerosive GERD Improvement in Overall GERD Symptoms* 71.2% (42/59) Erosive Esophagitis Improvement in Overall GERD Symptoms* 78.3% (18/23) Healing Rate 95.5% (21/22) Symptoms assessed by patient diary (parents/caregivers as necessary). No data available for five patients. Data from one healed patient was excluded from this analysis due to timing of final endoscopy. In these 87 adolescent patients, increases in serum gastrin levels were similar to those observed in adult studies, median fasting serum gastrin levels increased 42% from 45 pg/mL at baseline to 64 pg/mL at the final visit. (Normal serum gastrin levels are 25 to 111 pg/mL.) The safety of lansoprazole delayed-release capsules has been assessed in these 87 adolescent patients. Treatment-related dizziness, reported in this prescribing information as occurring in less than 1% of adult patients, was reported in this study by three adolescent patients with nonerosive GERD, who had dizziness concurrently with other reactions (such as migraine, dyspnea, and vomiting).

Juvenile Animal Toxicity Data Heart Valve Thickening In two oral toxicity studies, thickening of the mitral heart valve occurred in juvenile rats treated with lansoprazole. The treatment durations associated with heart valve thickening ranged from 5 days to 8 weeks. The findings reversed or trended towards reversibility after a 4-week drug-free recovery period.

Based on exposure margins, the risk of heart valve injury does not appear to be relevant to patients one year of age and older. Bone Changes In an eight-week oral toxicity study in juvenile rats with dosing initiated on postnatal Day 7, doses equal to or greater than 100 mg/kg/day (2.5 times the daily pediatric dose of 15 mg in children age one year to 11 years weighing 30 kg or less, based on AUC) produced delayed growth, with impairment of weight gain observed as early as postnatal Day 10 (age equivalent to neonatal humans). At the end of treatment, the signs of impaired growth at 100 mg/kg/day and higher included reductions in body weight (14 to 44% compared to controls), absolute weight of multiple organs, femur weight, femur length, and crown-rump length.

Femoral growth plate thickness was reduced only in males and only at the 500 mg/kg/day dose. The effects related to delayed growth persisted through the end of the four-week recovery period. Longer term data were not collected.

Lansoprazole delayed-release capsules are contraindicated in patients with known hypersensitivity to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria. Proton Pump Inhibitors (PPIs), including lansoprazole, are contraindicated with rilpivirine-containing products.

For information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with lansoprazole, refer to the CONTRAINDICATIONS section of their prescribing information. Patients receiving rilpivirine-containing products.

Lansoprazole is not removed from the circulation by hemodialysis. In one reported overdose, a patient consumed 600 mg of lansoprazole with no adverse reaction. Oral lansoprazole doses up to 5000 mg/kg in rats and in mice (about 675.7 times the 30 mg human dose based on BSA) did not produce deaths or any clinical signs.

In the event of over-exposure, treatment should be symptomatic and supportive. If over-exposure occurs, call your poison control center at 1-800-222-1222 for current information on the management of poisoning or over-exposure.