Description:
Indications and Clinical Use
Note: When used in combination with antimicrobials for the eradication of H. pylori, the product monograph for those agents should be consulted.
Oral Administration
Adults
PREVACID (lansoprazole delayed-release capsules), and PREVACID FasTab (lansoprazole delayed-release tablets) are indicated 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.
Healing of NSAID-Associated Gastric Ulcer; treatment of NSAID-associated gastric ulcer in patients who continue NSAID use. (Controlled studies did not extend beyond 8 weeks.)
Reduction of Risk of NSAID-Associated Gastric Ulcers in patients with a history of gastric ulcers who require to continue taking a NSAID. (A controlled study did not extend beyond 12 weeks.)
Symptomatic Gastroesophageal reflux disease (sGERD); treatment of heartburn and other symptoms associated with GERD.
Pathological hypersecretory conditions including Zollinger-Ellison Syndrome (see Dosage and Administration).
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 and Administration).
(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.)
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 delayed-release capsules and amoxicillin.
Table 1 summarizes the eradication rates for the H. pylori Triple Therapy treatment regimens.
Prevacid (Lansoprazole) Cautions:
SIDE EFFECTS that may occur while taking this medication include stomach pain and diarrhea.
Prevacid (Lansoprazole) Side Effects:
Symptomatic response to therapy with lansoprazole does not preclude the presence of gastric malignancy.
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 Clostridium 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.
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.
Carcinogenesis and Mutagenesis
Safety concerns of long-term treatment relate to hypergastrinemia, possible enterochromaffin-like (ECL) effect and carcinoid formation. ECL cell hyperplasia and gastric carcinoid tumours were observed in four 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/m2) basis, of a 50 kg person of average height (1.46 m2 body surface area) given the recommended human dose of 30 mg/day (22.2 mg/m2). Lansoprazole produced dose-related gastric entero-chromaffin-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 one 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 tumours 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 tumours (hepatocellular adenoma plus carcinoma). The tumour 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 two months of therapy. By one 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.
Gastrointestinal
When gastric ulcer is suspected, the possibility of malignancy should be excluded before therapy with lansoprazole delayed-release capsules or lansoprazole delayed-release tablets are instituted as treatment with these drugs may alleviate symptoms and delay diagnosis.
Genitourinary
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 one-year toxicity study.
These changes are associated with endocrine alterations which have not been, to date, observed in humans.
Hepatic/Biliary/Pancreatic
Use in 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 per day should not be administered unless there are compelling clinical indications. Dose reduction in patients with severe hepatic disease should be considered.
Immune
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.
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Only available by prescription.
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