Prevacid FDT

Prevacid FDT

lansoprazole

Manufacturer:

Takeda

Distributor:

DKSH
Full Prescribing Info
Contents
Lansoprazole.
Description
PREVACID FDT 30mg Tablets contains lansoprazole 30mg.
PREVACID FDT are white to yellowish white uncoated tablets with orange to dark brown speckles for oral administration containing the active ingredient, lansoprazole in the form of enteric-coated microgranules.
PREVACID FDT is a preparation of lansoprazole, a proton pump inhibitor.
PREVACID FDT displays strong and sustained inhibition of gastric acid secretion by suppressing the activity of (H+-K+)-ATPase which exists locally in the parietal cells of gastric mucosa and plays an important role as a proton pump.
Clinically, PREVACID FDT attains a rapid and high healing ratio against gastric ulcer and duodenal ulcer, and the usefulness of the drug has been proven. It has also been proven to be a useful drug for treatment of stomal ulcer, reflux esophagitis and Zollinger-Ellison syndrome.
Action
Pharmacology: Pharmacodynamics: Mechanism of Action: Lansoprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or histamine H2-receptor antagonist properties, but that suppress gastric acid secretion by specific inhibition of the (H+, K+)-ATPase enzyme system at the secretory surface of the gastric parietal cell. Because this enzyme system is regarded as the acid (proton) pump within the parietal cell, lansoprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated gastric acid secretion irrespective of the stimulus.
Serum Gastrin Effects: In over 2100 patients, median fasting serum gastrin levels increased 50% to 100% from baseline but remained within normal range after treatment with 15 to 60 mg of oral lansoprazole. These elevations reached a plateau within two months of therapy and returned to pretreatment levels within four weeks after discontinuation of therapy.
Increased gastrin causes enterochromaffin-like cell hyperplasia and increased serum CgA levels. The increased CgA levels may cause false positive results in diagnostic investigations for neuroendocrine tumors.
Available published evidence suggests that proton pump inhibitors should be discontinued 14 days prior to CgA measurements. This is to allow CgA levels that might be spuriously elevated following PPI treatment to return to reference range.
Pharmacokinetics: PREVACID FDT contains an enteric-coated granule formulation of lansoprazole. Absorption of lansoprazole begins only after the granules leave the stomach. Absorption is rapid, with mean peak plasma levels of lansoprazole occurring after approximately 1.7 hours. Peak plasma concentration of lansoprazole (Cmax) and the area under the plasma concentration curve (AUC) of lansoprazole are approximately proportional in doses from 15mg to 60mg after single-oral administration. Lansoprazole does not accumulate and its pharmacokinetics are unaltered by multiple dosing.
Absorption: The absorption of lansoprazole is rapid, with mean Cmax occurring approximately 1.7 hours after oral dosing, and relatively complete with absolute bioavailability over 80%. In healthy subjects, the mean (±SD) plasma half-life was 1.5 (±1.0) hours. Both Cmax and AUC are diminished by about 50% to 70% if the drug is given 30 minutes after food as opposed to the fasting condition. There is no significant food effect if the drug is given before meals.
Distribution: Lansoprazole is 97% bound to plasma proteins. Plasma protein binding is constant over the concentration range of 0.05 to 5.0μg/mL.
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. Lansoprazole is thought to be transformed into two active species which inhibit acid secretion by (H+, K+)ATPase within the parietal cell canaliculus, but are not present in the systemic circulation. The plasma elimination of half-life of lansoprazole does not reflect its duration of suppression of gastric acid secretion. Thus, the plasma elimination half-life is less than two hours, while the acid inhibitory effect lasts more than 24 hours.
Elimination: Following single-dose oral administration of lansoprazole, virtually no unchanged lansoprazole was excreted in the urine. In one study, after a single oral dose of 14C-lansoprazole, approximately one-third of the administered radiation was excreted in the urine and two-thirds was recovered in the feces. This implies a significant biliary excretion of the metabolites of lansoprazole.
Special Populations: Geriatric: The clearance of lansoprazole is decreased in the elderly, with elimination half-life increased approximately 50% to 100%. Because the mean half-life in the elderly remains between 1.9 to 2.9 hours, repeated once daily dosing does not result in accumulation of lansoprazole. Peak plasma levels were not increased in the elderly.
Pediatric: The pharmacokinetics of lansoprazole were studies in pediatric patients with GERD aged 12 to 17 years. In adolescent subjects aged 12 to 17 years, subjects were randomized to receive lansoprazole at 15mg or 30mg q.d. Mean Cmax and AUC values of lansoprazole was not affected by bodyweight or age; and nearly dose-proportional increases in Mean Cmax and AUC values were observed. Overall, lansoprazole pharmacokinetic patients aged 12 to 17 years were similar to those observed in healthy adult subjects.
Gender: In a study comparing 12 male and 6 female human subjects, no gender differences were found in pharmacokinetics and intragastric pH results.
Renal Insufficiency: In patients with severe renal insufficiency, plasma protein binding decreased by 1.0%-1.5% after administration of 60mg of lansoprazole. Patients with renal insufficiency had a shortened elimination half-life and decreased total AUC (free and bound). AUC for free lansoprazole in plasma, however, was not related to the degree of renal impairment, and Cmax and Tmax were not different from subjects with healthy kidneys. No dose adjustment is necessary in patients with renal insufficiency.
Hepatic Insufficiency: In patients with various degrees of chronic hepatic disease, the mean plasma half-life of the drug was prolonged from 1.5 hours to 3.2-7.2 hours. An increase in mean AUC of up to 500% was observed at steady state in hepatically-impaired patients compared to healthy subjects. Dose reduction in patients with severe hepatic disease should be considered.
Race: The pooled mean pharmacokinetic parameters of lansoprazole from twelve U.S. Phase 1 studies (N=513) were compared to the mean pharmacokinetic parameters from two Asian studies (N=20). The mean AUCs of lansoprazole in Asian subjects were approximately twice those seen in pooled U.S. data; however, the inter-individual variability was high. The Cmax values were comparable.
Indications/Uses
Gastric ulcer, duodenal ulcer, stomal ulcer and reflux esophagitis.
Relief of reflux-like symptoms (e.g. heartburn) and / or ulcer-like symptoms (e.g. upper epigastric pain) associated with acid-related dyspepsia.
Treatment and prophylaxis of NSAID-associated benign gastric ulcer, duodenal ulcers and relief of symptoms in patients requiring continued NSAID treatment.
Eradication of H. pylori from the upper gastrointestinal tract in patients with peptic ulcer (duodenal or benign gastric ulcer) when used in combination with appropriate antibiotics.
Zollinger-Ellison syndrome (and other Pathological hypersecretory conditions).
Short-term treatment of symptomatic GERD and erosive esophagitis for children (12-17 years of age).
Dosage/Direction for Use
Usually for adults, administer one tablet (30mg of lansoprazole) orally once a day.
In duodenal ulcer, 30mg once daily for 4 weeks. In gastric ulcer and stomal ulcer, 30mg once daily for 8 weeks. In reflux esophagitis, 30mg once daily for 4-8 weeks. In Zollinger-Ellison syndrome, the dosage should be adjusted according to the patient's signs and symptoms.
Eradication of H. pylori: The following combinations have been shown to be effective over 7 days. Prevacid tablet 30mg twice daily plus two of the following antibiotics: amoxicillin 1g twice daily or metronidazole 400mg twice daily and clarithromycin 250-500mg twice daily. The best eradication results are obtained when clarithromycin is combined with either amoxicillin or metronidazole. When used in combination with the recommended antibiotics, PREVACID FDT is associated with H. pylori - eradication rates of up to 90%.
Acid related dyspepsia: 30mg once daily for 2-4 weeks*.
Short term treatment of symptomatic GERD and Erosive Esophagitis (12-17 years): 30mg once daily for up to 8 weeks.
Treatment and prophylaxis of NSAID-associated benign gastric ulcers, duodenal ulcers and relief of symptoms in patients requiring continued NSAID treatment: 15 or 30mg once daily for 4-8 weeks for treatment **. Prophylaxis: 15 or 30mg once daily.
Renal impairment: Dose adjustment is not required in patients with impaired renal function. However, a daily dosage of 30mg should not be exceeded.
Hepatic impairment: Patients with moderate or severe liver disease should be kept under regular supervision and a 50% reduction of the daily dose is recommended.
Elderly: Ulcer healing rates in elderly patients are similar to those in a younger age group. The incidence rates of adverse events and laboratory test abnormalities are also similar to those seen in younger patients. For elderly patients, dosage and administration of lansoprazole need not be altered for a particular indication.
* PREVACID FDT 30mg once daily for 2-4 weeks depending on the severity and persistence of symptoms. Patients who do not respond after 4 weeks, or who relapse shortly afterwards, should be investigated.
** Most patients will be healed after 4 weeks; for those patients not fully healed, a further 4 weeks treatment can be given. For patients at particular risk or with ulcers that may be difficult to heal, the higher dose and / or the longer treatment duration should be used.

PREVACID FDT should not be chewed. Place the tablet on the tongue and allow it to disintegrate, with or without water, until the particles can be swallowed. The tablet typically disintegrates in less than 1 minute.
Alternatively, for children or other patients who have difficulty swallowing tablets, PREVACID FDT can be delivered in two different ways.
PREVACID FDT - Oral Syringe: For administration via oral syringe, PREVACID FDT can be administered as follows: Place a 15mg tablet in oral syringe and draw up approximately 4mL of water, or place a 30mg tablet in oral syringe and draw up approximately 10mL of water.
Shake gently to allow for quick dispersal.
After the tablet has dispersed, administer the contents within 15 minutes.
Refill the syringe with approximately 2mL (5mL for the 30mg tablet) of water, shake gently, and administer any remaining contents.
PREVACID FDT - Nasogastric Tube Administration (≥8 French): For administration via nasogastric tube, PREVACID FDT can be administered as follows: Place 15mg tablet in a syringe and draw up 4mL of water, or place a 30mg tablet in a syringe and draw up 10mL of water.
Shake gently to allow for a quick dispersal.
After the tablet has dispersed, inject through the nasogastric tube into the stomach within 15 minutes.
Refill the syringe with approximately 5mL of water, shake gently, and flush the nasogastric tube.
Overdosage
Oral doses up to 5000mg/kg in rats (approximately 1300 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. Lansoprazole is not removed from the circulation by hemodialysis. In one reported case of overdose, the patient consumed 600mg of lansoprazole with no adverse reaction.
Contraindications
PREVACID FDT is contraindicated in patients with known hypersensitivity to any of the formulation of PREVACID FDT.
Special Precautions
Before using PREVACID FDT with antibiotics to eradicate H. pylori, prescribers should refer to the full prescribing information of the respective antibiotic for guidance.
Careful administration: (PREVACID FDT should be administered with caution to the following patients.): Patients with a past history of drug hypersensitivity.
Elderly patients (See 5: Usage in the Elderly.)
Patients with impaired renal and hepatic function (See 6: Usage in impaired renal and hepatic function).
The possibility of malignancy should be excluded when gastric ulcer is suspected, as symptoms may be alleviated and diagnosis delayed.
Regular Surveillance: Patients on proton pump inhibitor treatment (particularly those treated for long term) should be kept under regular surveillance.
Subacute Cutaneous Lupus Erythematosus (SCLE): Proton pump inhibitors are associated in rare cases with the occurrence of subacute cutaneous lupus erythematosus (SCLE). If lesions occur, especially in sun exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical help promptly and the healthcare professional should consider stopping the product.
Bone fracture: PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long term PPI therapy (a year or longer). Observational studies suggest PPI may increase the overall risk of fracture by 10-40%. Some of this increase may be due to other risk factors. Patients at risk of osteoporosis should receive care according to current clinical guidelines and they should have an adequate intake of vitamin D and calcium.
Clostridium difficile: PPI therapy may be associated with an increased risk of Clostridium difficile associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve. Patients should use the lowest drug and shortest duration of PPI therapy appropriate to the condition being treated.
Hypomagnesemia: has rarely been reported in patients treated with PPIs for at least three months (in most cases after a year of therapy). Serious adverse events such as fatigue, tetany, delirium, convulsions, dizziness, arrhythmias and seizures. can occur but they may begin insidiously and be overlooked. In most affected patients, hypomagnesaemia improved after magnesium replacement and discontinuation of the PPI.
For patients expected to be on prolonged treatment or who take PPI with digoxin or drugs that may cause hypomagnesaemia (e.g. diuretics), health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment.
Influence on Vitamin B12 Absorption: Daily treatment with any acid-suppressing medications over a prolonged period of time (e.g. longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B12) caused by hypo- or achlorhydria. Cyanocobalamin deficiency should be considered in patients with Zollinger-Ellison syndrome and other pathological hypersecretory conditions requiring long-term treatment, individuals with reduced body stores or risk factors for reduced vitamin B12 absorption (such as the elderly) on long-term therapy or if relevant clinical symptoms are observed.
Interference with laboratory tests: Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, proton pump inhibitor treatment should be stopped 14 days before CgA measurements.
HIV Protease Inhibitors: Co-administration of lansoprazole is not recommended with HIV protease inhibitors for which absorption is dependent on acidic intragastric pH such as atazanavir, nelfinavir; due to significant reduction in their bioavailability.
Pregnancy (Category B) and Lactation: Pregnancy: Lansoprazole should be administered to pregnant women with caution only if needed.
Lactation: It is unknown whether lansoprazole is excreted in human breast milk. During treatment with lansoprazole, nursing should be avoided if the administration of this drug is necessary for the mother.
Use in children: 12 to 17 years of age: In an uncontrolled, open-label, U.S. multicenter study, 87 adolescent patients (12-17 years of age) with symptomatic GERD were treated with PREVACID FDT for 8 to 12 weeks. Baseline upper endoscopies classified these patients into two groups: 64 (74%) nonerosive GERD and 23 (26%) erosive esophagitis (EE). The nonerosive GERD patients received PREVACID FDT 15mg q.d. for 8 weeks and the EE patients received PREVACID FDT 30mg q.d. for 8 to 12 weeks. At baseline, 89% of these patients had mild to moderate overall GERD symptoms (assessed by investigator interviews). During 8 weeks of PREVACID FDT 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 8 weeks of PREVACID FDT treatment. One patient remained unhealed after 12 weeks of treatment. (See table.)

Click on icon to see table/diagram/image

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 45pg/mL at baseline to 64 pg/mL [interquartile range (25th - 75th percentile) of 44 - 88pg/mL] at the final visit. (Normal serum gastrin levels are 25 to 111pg/mL).
The safety of PREVACID FDT has been assessed in these 87 adolescent patients. Of the 87 adolescent patients with GERD, 6% (5/87) took PREVACID FDT for <6 weeks, 93% (81/87) for 6-10 weeks, and 1% (1/87) for >10 weeks.
The most frequently reported (at least 3%) treatment-related adverse events in these patients were headache (7%), abdominal pain (5%), nausea (3%) and dizziness (3%). Treatment-related dizziness, reported in this package insert as occurring in <1% of adult patients, was reported in this study by 3 adolescent patients with nonerosive GERD, who had dizziness concurrently with other events (such as migraine, dyspnea, and vomiting).
Use In Pregnancy & Lactation
Pregnancy (Category B) and Lactation: Pregnancy: Lansoprazole should be administered to pregnant women with caution only if needed.
Lactation: It is unknown whether lansoprazole is excreted in human breast milk. During treatment with lansoprazole, nursing should be avoided if the administration of this drug is necessary for the mother.
Adverse Reactions
Hypersensitivity: Anaphylactic reactions (generalized rash, facial edema, dyspnea, etc.) may rarely occur, and shock has consequently occurred in certain cases. Toxic epidermal necrolysis (Lyell syndrome) and oculomucocutaneous syndrome (Stevens-Johnson syndrome) may occur. Therefore, close observation should be made, and if any abnormality is observed, PREVACID FDT should be discontinued and appropriate measures taken. Rash and pruritus may infrequently occur.
Hepatic: Severe hepatic dysfunction with jaundice, hepatitis, etc., may rarely occur. Therefore, close observation should be made. If any abnormality is observed, PREVACID FDT should be discontinued and appropriate measures taken. The elevation of GOT, GPT, alkaline-P, LDH or γ-GTP may infrequently occur.
Blood: Agranulocytosis, pancytopenia or hemolytic anemia may rarely occur. Anemia, leucopenia, eosinophilia or thrombocytopenia may infrequently occur. Therefore, close observation should be made, and if any abnormality is observed, such appropriate measures as discontinuation of PREVACID FDT should be taken.
Gastrointestinal: Constipation, diarrhea, dry mouth or abdominal distension may infrequently occur.
Nausea, vomiting, microscopic colitis, anorexia, Fundic gland polyps (benign), abdominal pain, candidiasis, stomatitis, glossitis or taste abnormality may rarely occur. With the exception of patients being treated for the eradication of Helicobacter pylori infection, if diarrhea persists, administration of PREVACID FDT should be discontinued, due to the possibility of microscopic colitis with thickening of the collagen bundle or infiltration of inflammatory cells noted in the large intestine submucosa. In majority of cases, symptoms of microscopic colitis resolve on discontinuation of PREVACID FDT. Serious colitis accompanied with bloody stools, such as pseudomembranous colitis, may occur due to amoxicillin or clarithromycin being used for Helicobacter pylori eradication. If abdominal pain and frequent diarrhea occur, appropriate measures, such as immediate discontinuation of the treatment, should be taken. Heartburn and gastroesophageal reflux were observed (<1%) in the clinical studies on Helicobacter pylori eradication.
Psychoneurotic: Headache or sleepiness may infrequently occur. Depressed state, insomnia, dizziness or tremor may rarely occur.
Metabolism and nutrition disorders: Hypomagnesaemia, vitamin B12 deficiency.
Renal: Interstitial nephritis (with possible progression to renal failure).
Musculoskeletal disorders: Fracture of the hip, wrist or spine.
Skin and subcutaneous tissue disorders: Subacute cutaneous lupus erythematosus (SCLE).
Infections and infestations: Clostridium difficile associated diarrhea.
Others: Interstitial pneumonia may rarely occur. Therefore, if fever, coughing, dyspnea, abnormal lung sound (crepitation), etc., are observed such examinations as chest X-ray should immediately be performed, and PREVACID FDT should be discontinued. Appropriate measures, such as treatment with a corticosteroid preparation, should be taken. Fever or elevation of total cholesterol and uric acid may infrequently occur. Gynecomastia, blurred vision, edema, weakness, malaise, numbness of tongue or lips, numbness of limbs, arthralgia, muscle pain or alopecia may rarely occur. Increased triglyceride, positive urinary protein, or positive urine sugar were observed (1-5%) in the clinical studies on Helicobacter pylori eradication.
Drug Interactions
Lansoprazole is metabolized through the cytochrome P450 system, specifically through the CYP3A and CYP2C19 isozymes. Studies have shown that lansoprazole does not have clinically significant interactions with other drugs metabolized by the cytochrome P450 system such as warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propanolol, prednisolone, diazepam, clarithromycin, or terfenadine in healthy subjects. These compounds are metabolized through various cytochrome P450 isozymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A. When lansoprazole was administered concomitantly with theophylline (CYP1A2, CYP3A), a minor increase (10%) in the clearance of theophylline was seen. Because of the small magnitude and the direction of the effect on theophylline clearance, this interaction has not been considered to be clinically significant. Nonetheless, individual patients may require additional titration of their theophylline dosage when lansoprazole is started or stopped to ensure clinically effective blood levels.
In a study of healthy subjects neither the pharmacokinetics of warfarin enantiomers nor prothrombin time were affected following single or multiple 60mg doses of lansoprazole. However, there have been reports of increased International Normalized Ratio (INR) and prothrombin time in patients receiving proton pump inhibitors, including lansoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time. Lansoprazole has also been shown to have no clinically significant interaction with amoxicillin. In a single-dose crossover study examining lansoprazole 30mg and omeprazole 20mg each administered alone and concomitantly with sucralfate 1gram, absorption of the proton pump inhibitors was delayed and their bioavailability was reduced by 17% and 16%, respectively, when administered concomitantly with sucralfate. Therefore, proton pump inhibitors should be taken at least 30 minutes prior to sucralfate. In clinical trials, antacids were administered concomitantly with PREVACID FDT this did not interfere with its effect. 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).
HIV Protease Inhibitors: Co-administration of lansoprazole is not recommended with HIV protease inhibitors for which absorption is dependent on acidic intragastric pH such as atazanavir, nelfinavir; due to significant reduction in their bioavailability.
Methotrexate: Concomitant use with high-dose Methotrexate may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities.
Clopidogrel: Concomitant administration of lansoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition. No dose adjustment of clopidogrel is necessary when administered with an approved dose of lansoprazole.
Warfarin: Co-administration of lansoprazole 60 mg and warfarin did not affect the pharmacokinetics of warfarin or INR. However, there have been reports of increased INR and prothrombin time in patients receiving PPIs and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with lansoprazole and warfarin concomitantly may need to be monitored for increase in INR and prothrombin time
Tacrolimus: Concomitant administration of lansoprazole and tacrolimus may increase whole blood levels of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19.
Drugs that Inhibit or Induce CYP2C19: (Tacrolimus, Fluvoxamine): Concomitant administration of lansoprazole and tacrolimus may increase whole blood levels of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19. Inhibitors of CYP2C19 such as fluvoxamine would likely increase the systemic exposure of to lansoprazole. Inducers of CYP2C19 would likely decrease the systemic exposure to lansoprazole.
Caution For Usage
Instructions for use/handling: The tablets of PREVACID FDT is orally dispersed, but the ingredients are not absorbed through oral mucous membrane. Therefore, this tablet should be swallowed with saliva or water after placing the tablet on the tongue.
This product is more fragile compared with the tablets heretofore in use.
Use the tablet as soon as possible after unsealing, even before the expiration date.
Storage
Store below 30°C in the original packaging.
Shelf-Life: 3 years after manufacture.
ATC Classification
A02BC03 - lansoprazole ; Belongs to the class of proton pump inhibitors. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).
Presentation/Packing
FD tab 30 mg (white to yellowish white uncoated with orange to dark brown speckles) x 28's.
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