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PREVACID®
Abbott
Lansoprazole
H KATPase Inhibitor
Note: When used in combination with antimicrobials for the eradication of H. pylori, the product monograph for those agents should be consulted.
 
Action And Clinical Pharmacology: Lansoprazole inhibits the gastric H KATPase (the proton pump) which catalyzes the exchange of Hand K It is effective in the inhibition of both basal acid secretion and stimulated acid secretion.

In healthy subjects, single and multiple doses of lansoprazole (15 to 60 mg) have been shown in healthy subjects to decrease significantly basal gastric acid output and to increase significantly mean gastric pH and percent of time at pH >3 and 4. These doses have also been shown to reduce significantly meal-stimulated gastric acid output and gastric secretion volume. Single or multiple doses of lansoprazole (10 to 60 mg) reduced pentagastrin-stimulated acid output. In addition, lansoprazole has been demonstrated to reduce significantly basal and pentagastrin-stimulated gastric acid secretion among DU and hypersecretory patients, and basal gastric acid secretion among patients with GU disease.

A dose-response effect was analyzed by considering the results from clinical pharmacology studies that evaluated more than one dose of lansoprazole. The results indicated that, in general, as the dose was increased from 7.5 mg to 30 mg, there was a decrease in mean gastric acid secretion and an increase in the average time spent at higher pH values (pH >4).

The results of pharmacodynamic studies with lansoprazole in normal subjects suggest that doses of 7.5 to 10 mg are substantially less effective in inhibiting gastric acid secretion than doses of 15 mg or greater. In view of these results, the doses of lansoprazole evaluated in the principal clinical trials ranged from 15 to 60 mg daily.

Eradication of H. pylori: H. pylori is considered to be a major factor in the etiology of duodenal ulcer disease. The presence of H. pylori may damage the mucosal integrity due to the production of enzymes (catalase, lipases, phospholipases, proteases, and urease), adhesins and toxins; the inflammatory response generated in this manner contributes to mucosal damage.

The concomitant administration of an antimicrobial(s) and an antisecretory agent such as lansoprazole, improves the eradication of H. pylori as compared to individual drug administration. The higher pH resulting from antisecretory treatment, optimizes the environment for the pharmacologic action of the antimicrobial agent(s) against H. pylori.

Pharmacokinetics: Prevacid contains an enteric-coated granule formulation of lansoprazole to ensure that absorption of lansoprazole begins only after the granules leave the stomach (lansoprazole is acid-labile). Peak plasma concentrations of lansoprazole (Cmax and the area under the plasma concentration curve (AUC) of lansoprazole are approximately proportional in doses of 15 to 60 mg after single oral administration. Lansoprazole pharmacokinetics are unaltered by multiple dosing and the drug does not accumulate.

Lansoprazole is highly bioavailable when administered orally. In a definitive absolute bioavailability study, the absolute bioavailability was shown to be 86% for a 15 mg capsule and 80% for a 30 mg capsule. First pass effect is apparently minimal.

Absorption: Absorption is rapid, with mean peak plasma levels of lansoprazole occurring at approximately 1.7 hours. Peak plasma concentrations of lansoprazole (Cmax) and the area under the plasma concentration curve (AUC) are approximately proportional to dose throughout the range that has been studied (up to 60 mg).

Absorption With Food: Food reduces the peak concentration and the extent of absorption by about 50%. Moreover, the results of a pharmacokinetic study that compared the bioavailability of lansoprazole following a.m. dosing (fasting) versus p.m. dosing (3 hours after a meal) indicated that both Cmax and AUC values were increased by approximately 2-fold or more with a.m. dosing. Therefore, it is recommended that lansoprazole be administered in the morning prior to breakfast.

Absorption With Antacids: Simultaneous administration of lansoprazole with Maalox (aluminum and magnesium hydroxide) or Riopan (magaldrate) resulted in lower peak serum levels, but did not significantly reduce bioavailability of lansoprazole.

In a single-dose crossover study when 30 mg of lansoprazole was administered concomitantly with 1 g of sucralfate in healthy volunteers, absorption of lansoprazole was delayed and its bioavailability was reduced. The value of lansoprazole AUC was reduced by 17% and that for Cmax was reduced by 21%.

In a similar study when 30 mg of lansoprazole was administered concomitantly with 2 g of sucralfate, lansoprazole AUC and Cmax were reduced by 32% and 55%, respectively. When lansoprazole dosing occurred 30 minutes prior to sucralfate administration, Cmax was reduced by only 28% and there was no statistically significant difference in lansoprazole AUC. Therefore, lansoprazole may be given concomitantly with antacids but should be administered at least 30 minutes prior to sucralfate.

Distribution: Lansoprazole is 97% bound to plasma proteins. The mean total body clearance (Cl) of lansoprazole was calculated to be 31±8 L/hour, and the volume of distribution (Vss) was calculated to be 29±4 L.

Elimination: Following single dose oral administration of lansoprazole, virtually no unchanged lansoprazole was excreted in the urine. After a single dose of 4-lansoprazole, approximately one-third of the dose was excreted in the urine and approximately two-thirds were recovered in the feces. This implies a significant biliary excretion of the metabolites of lansoprazole.

Metabolism: Lansoprazole is extensively metabolized in the liver. Two metabolites have been identified in measurable quantities in plasma, the hydroxylated sulfinyl and sulfone derivatives of lansoprazole. These metabolites have very little or no antisecretory activity. Within the parietal cell canaliculus, lansoprazole is thought to be transformed into 2 active metabolites which inhibit acid secretion by (H K- ATPase, but these metabolites are not present in the systemic circulation. The plasma elimination half-life of lansoprazole does not reflect its duration of suppression of gastric acid secretion. Thus, the plasma elimination hlaf-life is less than 2 hours while the acid inhibitory effect lasts more than 24 hours.

Special Populations: Patients With Hepatic Impairment: As would be expected with a drug that is primarily metabolized by the liver, in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) chronic hepatic disease, the plasma 1.5 hours half-life of the drug increased to 5.2 hours compared to the 1.5 hours half-life in healthy subjects. An increase in AUC of 3.4 fold was observed in patients with hepatic impairment versus healthy subjects (7 096 versus 2 645 ng•h/mL) which was due to slower elimination of lansoprazole; however, Cmax was not significantly affected.

Patients With Renal Impairment: In patients with mild (Clcr 40 to 80 mL/min), moderate Clcr 20 to 40 mL/min) and severe (Clcr <20 mL/min) chronic renal impairment, the disposition of lansoprazole was very similar to that of healthy volunteers.

The impact of dialysis on lansoprazole was evaluated from a pharmacokinetic standpoint, and there were no significant differences in AUC, Cmax or t 1/2 between dialysis day and dialysis-free day. Dialysate contained no measurable lansoprazole or metabolite. Lansoprazole is not significantly dialyzed.

Geriatrics: The results from the studies that evaluated the pharmacokinetics of lansoprazole in an older population revealed that in comparison with younger subjects, older subjects exhibited significantly larger AUCs and longer t 1/2s. Lansoprazole did not accumulate in the older subjects upon multiple dosing since the longest mean t 1/2 in the studies was 2.9 hours, and lansoprazole is dosed once daily. Cmax in the elderly was comparable to that found in adult subjects.

Children: The pharmacokinetics of lansoprazole have not been investigated in patients <18 years of age.

Gender: In a study comparing 12 male and 6 female subjects, no gender differences were found in pharmacokinetics and intragastric pH results (see Precautions, Women).

Race: The pooled pharmacokinetic parameters of lansoprazole from 12 U.S. Phase I studies (N=513) were compared to the mean pharmacokinetic parameters from 2 Asian studies (N=20). The mean AUCs of lansoprazole in Asian subjects are approximately twice that seen in pooled US data, however, the inter-individual variability is high. The Cmax values are comparable.

Indications And Clinical Uses: In the treatment of conditions where a reduction of gastric acid secretion is required, such as: duodenal ulcer; gastric ulcer; reflux esophagitis including patients with Barrett's esophagus, and patients poorly responsive to an adequate course of therapy with histamine H2-receptor antagonists; pathological hypersecretory conditions including Zollinger-Ellison syndrome (see Dosage); eradication of H. pylori.

Triple Therapy: Lansoprazole, in combination with clarithromycin plus amoxicillin as triple therapy, is indicated for the treatment of patients with H. pylori infection and active duodenal ulcer disease. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence (see Dosage).

(For additional information on triple therapy for the treatment of H. pylori infection and active duodenal ulcer recurrence, refer to the Hp-PAC product monograph).

Dual Therapy: Lansoprazole, in combination with amoxicillin as dual therapy, are indicated for the treatment of patients with H. pylori infection and active duodenal ulcer disease who are either allergic or intolerant to clarithromycin or in whom resistance is known or suspected. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence (see Dosage).

In patients with a recent history of duodenal ulcers who are H. pylori positive, eradication therapy may reduce the rate of recurrence of duodenal ulcers. The optimal timing for eradication therapy for such patients remains to be determined.

In patients who fail a therapy combination containing clarithromycin, susceptibility testing should be done. If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, an alternative therapy combination is recommended.

Resistance to amoxicillin has not been demonstrated in clinical studies with lansoprazole and amoxicillin.

Contra-Indications: In patients with known hypersensitivity to any component of the formulation.

Amoxicillin is contraindicated in patients with a known hypersensitivity to any penicillin. (Please refer to the amoxicillin Product Monograph before prescribing).

Clarithromycin is contraindicated in patients with known hypersensitivity to clarithromycin, erythromycin or other macrolide antibacterial agents. Clarithromycin is also contraindicated in patients receiving concurrent therapy with astemizole, terfenadine, cisapride or pimozide. (Please refer to the Clarithromycin tablets Product Monograph before prescribing).

Manufacturers' Warnings In Clinical States: Clarithromycin should not be used in pregnancy except where no alternative therapy is appropriate, particularly during the first 3 months of pregnancy. If pregnancy occurs while taking the drug, the patient should be apprised of the potential hazard to the fetus. Clarithromycin has demonstrated adverse effects on pregnancy outcome and/or embryo-fetal development in monkeys, mice, rats and rabbits at doses that produced plasma levels 2 to 17 times the serum levels obtained in humans treated at the maximum recommended doses (see Warnings section in the clarithromycin product monograph).

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including clarithromycin and amoxicillin, 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.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by C. difficile is a primary cause of "antibiotic-associated colitis".

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug effective against C. difficile.

Allergic reactions (including anaphylaxis) have been reported in patients receiving clarithromycin orally.

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. These reactions are more apt to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens.

There have been well documented reports of individuals with a history of penicillin hypersensitivity reactions who have experienced severe hypersensitivity reactions when treated with a cephalosporin. Before initiating therapy with any penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, and other allergens. If an allergic reaction occurs, amoxicillin should be discontinued and the appropriate therapy instituted.

Serious anaphylactic reactions require immediate emergency treatment with epinephrine, oxygen, corticosteroids, and airway management, including intubation, as indicated.

When gastric ulcer is suspected the possibility of malignancy should be excluded before therapy with lansoprazole is instituted as treatment with this drug may alleviate symptoms and delay diagnosis.

Pregnancy: There are no adequate or well-controlled studies in pregnant women. Therefore, lansoprazole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Reproductive studies conducted in pregnant rats at oral doses up to 150 mg/kg/day (40 times the recommended human dose based on body surface area), and in rabbits at oral doses up to 30 mg/kg/day (16 times the recommended human dose based on body surface area), did not disclose any evidence of a teratogenic effect. Maternal toxicity and a significant increase in fetal mortality were observed in the rabbit study at doses above 10 mg/kg/day. In rats, maternal toxicity and a slight reduction in litter survival and weights were noted at doses above 100 mg/kg/day.

Lactation: It is not known whether lansoprazole is excreted in human milk. Because drugs are excreted in human milk, it should not be given to nursing mothers unless its use is considered essential.

Children: Safety and effectiveness in children have not been established.

Patients With Hepatic Impairment: It is recommended that the initial dosing regimen need not be altered for patients with mild or moderate liver disease, but for patients with moderate impairment, doses higher than 30 mg/day should not be administered unless there are compelling clinical indications.

Precautions: General: Symptomatic response to therapy with lansoprazole does not preclude the presence of gastric malignancy.

H. pylori Eradication and Compliance: To avoid failure of the eradication treatment with a potential for developing antimicrobial resistance and a risk of failure with subsequent therapy, patients should be instructed to follow closely the prescribed regimen.

For the eradication of H. pylori, amoxicillin and clarithromycin should not be administered to patients with renal impairment since the appropriate dosage in this patient population has not yet been established.

Carcinogenicity: Safety concerns of long-term treatment relate to hypergastrinemia, possible ECL effect and carcinoid formation. ECL cell hyperplasia and gastric carcinoid tumors were observed in 4 animal studies.

In two 24-month carcinogenicity studies, Sprague-Dawley rats were treated orally with doses of 5 to 150 mg/kg/day about 1 to 40 times the exposure on a body surface (mg/m basis, of a 50 kg person of average height (1.46 mbody surface area) given the recommended human dose of 30 mg/day (22.2 mg/m. Lansoprazole produced dose-related gastric enterochromaffin-like (ECL) cell hyperplasia and ECL cell carcinoids in both male and female rats. It also increased the incidence of intestinal metaplasia of the gastric epithelium in both sexes. In male rats lansoprazole produced a dose related increase of testicular interstitial cell adenomas. The incidence of these adenomas in rats receiving doses of 15 to 150 mg/kg/day (4 to 40 times the recommended human dose based on body surface area) exceeded the low background incidence (range=1.4 to 10%) for this strain of rats. Testicular interstitial cell adenoma also occurred in 1 of 30 rats treated with 50 mg/kg/day (13 times the recommended human dose based on body surface area) in a 1-year toxicity study.

In a 24-month carcinogenicity study, CD-1 mice were treated orally with doses of 15 to 600 mg/kg/day, 2 to 80 times the recommended human dose based on body surface area. Lansoprazole produced a dose-related increased incidence of gastric ECL cell hyperplasia. Lansoprazole also induced a low, non-dose-related incidence of carcinoid tumors in the gastric mucosa in several dose groups (one female mouse in the 15 mg/kg/day group, one male mouse in the 150 mg/kg/day group, and 2 males and 1 female in the 300 mg/kg/day group). It also produced an increased incidence of liver tumors (hepatocellular adenoma plus carcinoma). The tumor incidences in male mice treated with 300 and 600 mg/kg/day (40 to 80 times the recommended human dose based on body surface area) and female mice treated with 150 to 600 mg/kg/day (20 to 80 times the recommended human dose based on body surface area) exceeded the ranges of background incidences in historical controls for this strain of mice. Lansoprazole treatment produced adenoma of rete testis in male mice receiving 75 to 600 mg/kg/day (10 to 80 times the recommended human dose based on body surface area).

Analysis of gastric biopsy specimens from patients after short-term treatment of proton pump inhibitors have not detected ECL cell effects similar to those seen in animal studies. Longer term studies in humans revealed a slight increase in the mean ECL-cell density, although there was no microscopic evidence of cell hyperplasia. Similar results were seen in the maintenance treatment studies, where patients received up to 15 months of lansoprazole therapy. Serum gastrin values increased significantly from their baseline values but reached a plateau after 2 months of therapy. By 1 month post-treatment, fasting serum gastrin values returned to lansoprazole therapy baseline. Moreover, results from gastric biopsies from short-term, long-term and maintenance treatment studies indicate that there are no clinically meaningful effects on gastric mucosa morphology among lansoprazole-treated patients.

Retinal Atrophy: In animal studies, retinal atrophy was observed in rats dosed orally for 2 years with lansoprazole at doses of 15 mg/kg/day and above. These changes in rats are believed to be associated with the effects of taurine imbalance and phototoxicity in a susceptible animal model. Clinical data available from long-term lansoprazole studies are not suggestive of any drug-induced eye toxicity in humans. In humans, there are presently no concerns for ocular safety with short-term lansoprazole treatment and the risks associated with long-term use for nearly 5 years appear to be negligible. The finding of drug-induced retinol atrophy in the albino rat is considered to be species-specific with little relevance for humans.

Leydig Cell Hyperplasia/Leydig Cell Tumors: In the 24-month toxicology study in rats, after 18 months of treatment, Leydig cell hyperplasia increased above the concurrent and historical control level at dosages of 15 mg/kg/day or higher.

Testicular interstitial cell adenoma also occurred in 1 of 30 rats treated with 50 mg/kg/day (13 times the recommended human dose based on body surface area) in a 1-year toxicity study.

These changes are associated with endocrine alterations which have not been, to date, observed in humans.

Drug Interactions: Lansoprazole is metabolized through the cytochrome P450 system, specifically through CYP3A and CYP2C19. Studies have shown that lansoprazole does not have clinically significant interactions with warfarin, antipyrine, indomethacin, ASA, ibuprofen, phenytoin, prednisone, antacids (Maalox and Riopan), diazepam clarithromycin, propranolol, amoxicillin or terfenadine in healthy subjects. These compounds are metabolized through various cytochrome P450 isozymes including CYP1A2, CYP2C19, CYP2D6 and CYP3A. When lansoprazole was administered concomitantly with theophylline CYP1A2, CYP3A, a minor increase (10%) in the clearance of theophylline was seen, which is unlikely to be of clinical concern. Nonetheless, individual patients may require adjustment of their theophylline dosage when lansoprazole is started or stopped to ensure clinically effective blood levels.

In a single-dose crossover study when 30 mg of lansoprazole was administered concomitantly with 1 g of sucralfate in healthy volunteers, absorption of lansoprazole was delayed and its bioavailability was reduced. The value of lansoprazole AUC was reduced by 17% and that for Cmax was reduced by 21%.

In a similar study when 30 mg of lansoprazole was administered concomitantly with 2 g of sucralfate, lansoprazole AUC and Cmax were reduced by 32% and 55%, respectively. When lansoprazole dosing occurred 30 minutes prior to sucralfate administration, Cmax was reduced by only 28% and there was no statistically significant difference in lansoprazole AUC. Therefore, lansoprazole may be given concomitantly with antacids but should be administered at least 30 minutes prior to sucralfate.

Lansoprazole causes a profound and long lasting inhibition of gastric acid secretion; therefore, it is theoretically possible that lansoprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (e.g., ketoconazole, ampicillin esters, iron salts, digoxin).

Combination Therapy With Clarithromycin and/or Amoxicillin: For more information on drug interactions for clarithromycin and amoxicillin, refer to their respective Product Monographs, under Precautions, Drug Interactions.

Antibiotic Resistance in Relation to H. pylori Eradication: Three patients 3/82 (3.7%) who had isolates susceptible to clarithromycin pretreatment and were treated with the triple therapy regimen remained H. pylori positive posttreatment. None of the isolates from these 3 patients had susceptibility results available after treatment with triple therapy; therefore, it is unknown whether or not these patients developed resistance to clarithromycin. Sixteen percent of the patients treated with the dual therapy regimen developed clarithromycin resistance post-treatment. Therefore, development of clarithromycin resistance should be considered as a possible risk.

Patients With Renal Impairment: No dosage modification of lansoprazole is required in patients with renal insufficiency.

Geriatrics: Ulcer healing rates in elderly patients are similar to those in younger age groups. The incidence rates of adverse events and laboratory test abnormalities are also similar to those seen in other age groups. The initial dosing regimen need not be altered for elderly patients, but subsequent doses higher than 30 mg/day should not be administered unless additional gastric acid suppression is necessary.

Women: Over 800 women were treated with lansoprazole. Ulcer healing rates in females are similar to those in males. The incidence rates of adverse events are also similar to those seen in males.

Adverse Reactions: Worldwide, over 7 000 patients have been treated with lansoprazole during Phase II and III short-term and long-term clinical trials involving various dosages and duration of treatment. In general, lansoprazole treatment has been well tolerated.

Short-term Studies: The following adverse events were reported to have a possible or probable relationship to drug as described by the treating physician in 1% or more of lansoprazole-treated patients who participated in placebo- and positive-controlled trials (see Tables III and IV). Numbers in parentheses indicate the percentage of the adverse events reported.

In the TAP Safety Database, all short-term, Phase II/III studies, one or more treatment-emergent Adverse Events (AEs) were reported by 715/1 359 (52.6%) Prevacid-treated patients; of those considered to be possibly or probably treatment-related AEs, one or more were reported by 276/1 359 (20.3%) Prevacid-treated patients. In all short-term, Phase II/III studies, one or more treatment-emergent AEs were reported by 150/254 (59.1%) placebo-treated patients; of those considered to be possibly or probably treatment-related AEs, one or more were reported by 56/254 (22%).

The most frequent AEs reported in the European short-term studies were diarrhea (3.3%), laboratory test abnormal (2.3%), headache (1.5%), constipation (1.2%), asthenia (1.1%), dizziness (1.1%), and abdominal pain (1.0%). The most frequent AEs reported in the Asian short-term studies were unspecified laboratory test abnormalities (7.3%), eosinophilia (1.0%) and increased ALT (1.0%).

Maintenance Studies: US Studies: Treatment-emergent adverse effects with an incidence of at least 2% in any treatment group of the maintenance treatment studies occurring from the start of maintenance treatment to the first recurrence of disease are displayed by body system and COSTART term, and by treatment group in Table V.

There were no frequently reported (³2%, incidence) severe adverse effects in the treatment-emergent or the possibly/probably treatment-related event categories with onset at any point from the start of maintenance treatment to the time of first recurrence of disease.

The adverse effects reported by at least 1% of patients receiving lead-in open-label lansoprazole treatment in long-term European Studies are diarrhea (5.7%), esophagitis (2.5%), abdominal pain (2.1%), gastritis (2.1%), flatulence (1.3%), headache (1.1%), constipation (1.0%), and nausea (1.0%). The incidence of adverse effects reported in the lead-in open-label period of the European Studies was similar to that seen in controlled studies; however, the overall incidence was lower for the lead-in open-label studies than for the H2-receptor antagonist controlled studies (27.5% versus 49.8%, respectively).

Additional adverse experiences occurring in <1% of patients or subjects in domestic and/or international trials, or occurring since the drug was marketed, are shown below within each body system.

Body as a Whole: asthenia, candidiasis, chest pain (not otherwise specified), edema, fever, flu syndrome, halitosis, infection (not otherwise specified), malaise, carcinoma, general pain.

Cardiovascular: angina, cerebrovascular accident, hypertension/hypotension, myocardial infarction, palpitations, shock (circulatory failure), vasodilation.

Digestive: melena, cholelithiasis, abnormal stools/melena, bezoar, constipation, dry mouth/thirst, flatulence, gastroenteritis, gastrointestinal hemorrhage, hematemesis, anorexia, increased appetite, increased salivation, rectal hemorrhage, cardiospasm, dyspepsia, dysphagia, eructation, esophageal stenosis, esophageal ulcer, esophagitis, stomatitis, fecal discoloration, tenesmus, ulcerative colitis, gastric nodules/fundic gland polyps, carcinoid.

Endocrine: diabetes mellitus, goiter, hyperglycemia/hypoglycemia.

Hematologic and Lymphatic*: agranulocytosis, anemia, aplastic anemia, hemolysis, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia and thrombotic thrombocytopenic purpura.

Metabolic and Nutritional Disorders: gout, weight gain/loss, edema.

Musculoskeletal: arthritis/arthralgia, musculoskeletal pain, myalgia.

Nervous System: agitation, amnesia, apathy, confusion, dizziness, syncope, hallucinations, hostility aggravated, libido decreased, depression, hemiplegia, insomnia, somnolence, thinking abnormality, anxiety, nervousness, paresthesia.

Respiratory: asthma, bronchitis, cough increased, dyspnea, hemoptysis, hiccup, upper respiratory inflammation/infection, pneumonia, epistaxis.

Skin and Appendages: acne, pruritus, rash, urticaria, alopecia.

Special Senses: amblyopia, eye pain, visual field defect, tinnitus, ophthalmologic disorders, ear disorder, deafness, otitis media, taste perversion.

Urogenital: abnormal menses, albuminuria, breast enlargement/gynecomastia, breast tenderness, glycosuria, impotence, kidney calculus, hematuria, urinary urgency.

*The majority of hematologic cases received were foreign-sourced and their relationship to lansoprazole was unclear.

Combination Therapy With Clarithromycin and Amoxicillin: In clinical trials using combination therapy with lansoprazole plus clarithromycin and amoxicillin, and lansoprazole plus amoxicillin, no adverse reactions related to these drug combinations were observed. Adverse reactions that have occurred have been limited to those that have been previously reported with lansoprazole, clarithromycin, or amoxicillin.

For more information on adverse reactions with clarithromycin or amoxicillin, refer to their respective Product Monographs, under the Adverse Effects section.

Triple Therapy: Lansoprazole/clarithromycin/amoxicillin: The most frequently reported adverse events for patients who received triple therapy were diarrhea (7%), headache (6%), and taste perversion (5%). No treatment-emergent adverse events were observed at significantly higher rates with triple therapy than with any dual therapy regimen.

Dual Therapy: Lansoprazole/amoxicillin: The most frequently reported adverse events for patients who received lansoprazole t.i.d. plus amoxicillin t.i.d. dual therapy were diarrhea (8%) and headache (7%). No treatment-emergent adverse events were observed at significantly higher rates with lansoprazole t.i.d. plus amoxicillin t.i.d. dual therapy than with lansoprazole alone.

Laboratory Values: In addition, the following changes in laboratory parameters were reported as adverse events. Abnormal liver function tests, increased AST, increased ALT, increased creatinine, increased alkaline phosphatase, increased gamma globulins, increased GGTP, increase/decreased/abnormal WBC, abnormal AG ratio, abnormal RBC, bilirubinemia, eosinophilia, hyperlipemia, increased/decreased electrolytes, increased/decreased cholesterol, increased glucocorticoids, increased LDH, increased/decreased/abnormal platelets, and increased gastrin levels. Additional isolated laboratory abnormalities were reported.

In the placebo controlled studies, when AST and ALT were evaluated, 0.4% (1/250) placebo patients and 0.3% (2/795) lansoprazole patients had enzyme elevations greater than 3 times the upper limit of normal range at the final treatment visit. None of these patients reported jaundice at any time during the study.

For more information on laboratory value changes with clarithromycin or amoxicillin, refer to their respective Product Monographs, under the Adverse Effects section.

Postmarketing Experience: Hypersensitivity reactions have been reported, including anaphylaxis.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: As in all cases where overdosing is suspected, treatment should be supportive and symptomatic. Any unabsorbed material should be removed from the gastrointestinal tract, and the patient should be carefully monitored. Lansoprazole is not removed from the circulation by hemodialysis. In one reported case of overdose, the patient consumed 600 mg of lansoprazole with no adverse reaction.

Oral doses up to 5 000 mg/kg in rats (approximately 1 300 times the recommended human dose based on body surface area) and mice (about 675.7 times the recommended human dose based on body surface area) did not produce deaths or any clinical signs.

Dosage And Administration: Duodenal Ulcer: The recommended adult oral dose is 15 mg daily before breakfast for 2 to 4 weeks (see Indications).

A small percentage of patients that are H. pylori negative will experience a disease recurrence and will require maintenance treatment with an antisecretory agent. Lansoprazole 15 mg daily before breakfast may be used up to 1 year for the maintenance treatment of recurrent duodenal ulcers.

H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence: Triple Therapy: lansoprazole/clarithromycin/amoxicillin. The recommended adult oral dose is 30 mg lansoprazole, 500 mg clarithromycin, and 1 g amoxicillin, all given twice daily for 14 days (see Indications). Daily doses should be taken before meals.

(For additional information on triple therapy for the treatment of H. pylori infection and active duodenal ulcer recurrence, refer to the Hp-PAC product monograph).

Dual Therapy: Lansoprazole/amoxicillin: The recommended adult oral dose is 30 mg lansoprazole and 1 g amoxicillin, each given 3 times daily for 14 days (see Indications). Daily doses should be taken before meals.

Optimal therapeutic regimens consisting of a shorter treatment duration for the eradication of H. pylori are currently under investigation.

For the eradication of H. pylori, amoxicillin and clarithromycin should not be administered to patients with renal impairment since the appropriate dosage in this patient population has not yet been established.

Gastric Ulcer: The recommended adult oral dose is 15 mg daily before breakfast for 4 to 8 weeks.

No dosage adjustment is necessary in patients with renal insufficiency. No dosage adjustment is necessary in the initial lansoprazole dosing regimen in older patients and in patients with mild to moderate hepatic impairment. Dosing recommendations described in the labelling should be adhered to for older patients and hepatically impaired patients.

Lansoprazole is not indicated for maintenance therapy in the treatment of patients with gastric ulcer.

Reflux Esophagitis or Poorly Responsive Reflux Esophagitis including Patients with Barrett's Esophagus: The recommended adult oral dose is 30 mg daily before breakfast for 4 to 8 weeks (see Indications).

Maintenance Treatment of Healed Reflux Esophagitis: For the long-term management of patients with healed reflux esophagitis, 15 mg lansoprazole given once daily before breakfast has been found to be effective in controlled clinical trials of 12 month's duration.

The recommended adult oral dose of lansoprazole for maintenance treatment of patients with healed reflux esophagitis is 15 mg daily before breakfast (see Indications).

Treatment and Maintenance of Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome: The dosage of lansoprazole in patients with pathologic hypersecretory conditions varies with the individual patient. The recommended adult oral starting dose is 60 mg once a day. Doses should be adjusted to individual patient needs and should continue for as long as clinically indicated. Dosages up to 90 mg b.i.d. have been administered. Daily dosage of greater than 120 mg should be administered in divided doses. Some patients with Zollinger-Ellison syndrome have been treated continuously with lansoprazole for more than 4 years.

Patients With Hepatic Impairment: The daily dose of lansoprazole should not exceed 30 mg (see Warnings).

Patients With Renal Impairment: No dosage modification of lansoprazole is necessary (see Precautions).

Geriatrics: The daily dose should not exceed 30 mg (see Precautions).

Concomitant Antacid Use: Simultaneous administration of lansoprazole with Maalox (aluminum and magnesium hydroxide) or Riopan (magaldrate) results in lower peak plasma levels, but does not significantly reduce bioavailability. Antacids may be used concomitantly if required. If sucralfate is to be given concomitantly, lansoprazole should be administered at least 30 minutes prior to sucralfate (see Pharmacology, Absorption With Antacids). In clinical trials, antacids were administered concomitantly with lansoprazole delayed-release capsules; this did not interfere with its effects.



Availability And Storage: 15 mg: Each pink and green-colored, opaque, hard gelatin, delayed-release capsule of enteric-coated granules contains: lansoprazole 15 mg. Nonmedicinal ingredients: cellulosic polymers, colloidal silicon dioxide, D&C Red No. 28, FD&C Blue No. 1, FD&C Green No. 3, FD&C Red No. 40, gelatin, magnesium carbonate, methacrylic acid copolymer, polyethylene glycol, polysorbate 80, starch, sucrose, sugar spheres, talc and titanium dioxide. Bottles of 30 and 100.

30 mg: Each pink and black-colored, opaque, hard gelatin, delayed-release capsule of enteric-coated granules contains: lansoprazole 30 mg. Nonmedicinal ingredients: cellulosic polymers, colloidal silicon dioxide, D&C Red No. 28, FD&C Blue No. 1, FD&C Red No. 40, gelatin, magnesium carbonate, methacrylic acid copolymer, polyethylene glycol, polysorbate 80, starch, sucrose, sugar spheres, talc and titanium dioxide. Bottles of 30 and 100.

Store in a tight container protected from light and moisture. Store between 15 and 25°C.