Lansoprazole

369.36

369.36

2017-001-1

758710|758638

DTXSID4023200

White to brownish-white crystalline powder

A02BC03|A - Alimentary tract and metabolism

29339900

87.1

2.8

off-white powder

1.50±0.1 g/cm3(Predicted)

178-182 °C (decomp)

555.8±60.0 °C(Predicted)

289.9±32.9 °C

1.635

Practically insoluble in water, soluble in anhydrous ethanol, very slightly soluble in acetonitrile.

2-8°C

2.55E-10mmHg at 25°C

Odorless

pKa1 = 1.1; pKa2 = 6.9; pKa3 = 12 /Estimated/

185.8 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

NONH for all modes of transport

2

36/37/38

26-36

DD9487500

Xi

P305 + P351 + P338

H315-H319-H335

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl lansoprazole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Warning|H315 (97.96%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 197 companies from 16 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

The most commonly reported adverse events occurring more frequently in lansoprazole treated patients compared to placebo include abdominal pain, constipation, diarrhea, and nausea. There is a case report of toxic epidermal necrolysis (TEN), which is a rare but very serious cutaneous reaction, caused by lansoprazole. The previously healthy patient presented with symptoms of TEN 15 days after starting lansoprazole to manage peptic disease. Although the use of PPI's is rarely associated with TEN, causation should be considered if a patient presents with TEN shortly after newly commencing a PPI. In a single case report, a patient ingested 600 mg of lansoprazole and did not experience any adverse effects or symptoms of overdose. Overall, lansoprazole is well tolerated with relatively few adverse effects. Lansoprazole is classified as Pregnancy Category B. Although there are animal studies that suggest lansoprazole does not cause harm to the fetus, there is still a paucity of human data. Hence, lansoprazole should only be administered to pregnant women if other options with more safety data have been exhausted. It is unknown if lansoprazole is excreted in human breast milk. It is worth mentioning that lansoprazole has been used safely in infants, and is therefore likely safe to use during breastfeeding.

Despite its wide use, lansoprazole has only rarely been associated with hepatic injury. In large scale, long term trials of lansoprazole, serum ALT elevations have occurred in less than 1% of patients and at rates similar to those that occur with placebo or comparator drugs. Only a small number of cases of clinically apparent liver disease due to lansoprazole or dexlansoprazole have been published and most have been anicteric and mild. In most instances, the time to onset was within 2 to 4 weeks and the pattern of enzyme elevations was hepatocellular or mixed. Hypersensitivity reactions with fever, rash and eosinophilia have been described due to dexlansoprazole and lansoprazole, and these reactions may be accompanied by minor serum enzyme elevations and thus qualify for DRESS syndrome (drug-rash with eosinophilia and systemic symptoms). Autoantibody formation is rare. Recovery is usually rapid (within a month) and complete upon stopping lansoprazole. Recurrence on reexposures has been reported.

Possible interactions of lansoprazole with medications known to be metabolized by the hepatic cytochrome p450 enzyme system should be considered.|... Lansoprazole, by increasing gastric pH, as the potential to affect the bioavailability of any medication whose absorption is pH-dependent. Also, lansoprazole may prevent the degradation of acid-labile drugs.|Lansoprazole causes prolonged inhibition of gastric acid secretion, and thereby my interfere with the absorption of these medications /ampicillin ester, digoxin, iron salts, ketoconazole/and other for which bioavailability is determined by gastric pH.|Lansoprazole appears to produce a dose-dependent decrease in the absorption of cyanocobalamin; this my be due to lansoprazole-induced hypochlorhydria or achlorhydria.|For more Interactions (Complete) data for LANSOPRAZOLE (9 total), please visit the HSDB record page.

97% of lansoprazole is plasma protein bound.

It is not known whether lansoprazole is distributed into breast milk. However, lansoprazole or its metabolites are distributed into the milk of rats.

Lansoprazole is used to reduce gastric acid secretion and is approved for short term treatment of active gastric ulcers, active duodenal ulcers, erosive reflux oesophagitis, symptomatic gastroesophageal reflux disease, and non-steroidal anti-inflammatory drug (NSAID) induced gastric and duodenal ulcers. It may be used in the maintenance and healing of several gastric conditions including duodenal ulcers, NSAID related gastric ulcers, and erosive esophagitis. Lansoprazole prevents recurrence of gastric ulcers in patients who have a documented history of gastric ulcers who also use NSAIDs chronically. Predictably, it is also useful in the management of hypersecretory conditions including Zollinger-Ellison syndrome. Lansoprazole is effective at eradicating H. pylori when used in conjunction with amoxicillin and clarithromycin (triple therapy) or with amoxicillin alone (dual therapy).|FDA Label

Lansoprazole is a proton pump inhibitor (PPI) and a potent inhibitor of gastric acidity which is widely used in the therapy of gastroesophageal reflux and peptic ulcer disease. Dexlansoprazole is an isomer of lansoprazole that has a similar spectrum of activity and toxicities. Lansoprazole therapy is associated with a low rate of transient and asymptomatic serum aminotransferase elevations and is a reported, but very rare cause of clinically apparent liver injury.

Antiulcer Agents

Antiulcerative|Lansoprazole is indicated for the short-term treatment of heartburn and other symptoms associated with gastroesophageal reflux disease (GERD). Lansoprazole is indicated for the short-term (up to 8 weeks) treatment for symptom relief and healing of all grades of erosive esophagitis (associated with GERD). Lansoprazole may be indicated for an additional 8 weeks of treatment of patients in whom healing has not occurred. If erosive esophagitis recurs, an additional course of lansoprazole treatment may be considered. Lansoprazole also is indicated to maintain healing of erosive esophagitis. /Included in US product labeling/|Lansoprazole is indicated for short-term (up to 8 weeks) treatment in patients with active benign gastric ulcer. /Included in US product labeling/|Lansoprazole is indicated for short-term (up to 4 weeks) treatment for symptom relief and healing in patients with active duodenal ulcer. Lansoprazole also is indicated to maintain healing of duodenal ulcers. /Included in US product labeling/|For more Therapeutic Uses (Complete) data for LANSOPRAZOLE (6 total), please visit the HSDB record page.

Worldwide, over 10,000 patients have been treated with lansoprazole in Phase 2-3 trials involving various dosages and durations of treatment. The adverse reaction profiles for prevacid delayed-release capsules and prevacid for delayed-release oral suspension are similar. In general, lansoprazole treatment has been well-tolerated in both short-term and long-term trials. ... The most commonly reported possibly or probably treatment-related adverse event during maintenance therapy was diarrhea.|An 85-year-old white man presented with an upper gastrointestinal hemorrhage from a gastric ulcer. His platelet count was normal on admission. He was started on oral lansoprazole 60 mg twice daily and, on hospital day 2, his platelet count decreased to 102 x 10(3)/mm(3); on hospital day 3, the platelet count was 36 x 10(3)/mm(3). Lansoprazole was discontinued, and the platelet count returned to normal. He has not had any further episodes of thrombocytopenia to date. After exclusion of other causes, the onset of thrombocytopenia after administration of lansoprazole, the resolution of the adverse reaction after discontinuation of the drug, and the fact that no other medicines were introduced during this time frame lead us to believe that this was most likely an idiosyncratic thrombocytopenic response to lansoprazole. To date, this is the first reported case of what appears to be isolated thrombocytopenia associated with lansoprazole.|Studies in elderly patients indicate that the clearance of lansoprazole is decreased in the elderly, resulting in a 50 to 100% increase in the elimination half-life. Because the mean half-life in the elderly remains between 1.9 and 2.9 hours, repeated once-daily dosing does not result in accumulation of lansoprazole. However, subsequent doses higher than 30 mg a day should not be administered unless additional gastric acid suppression is necessary.|Diarrhea is one of the most frequently reported adverse events during proton pump inhibitor use in any setting. Because of the limited available information, this study was set up with the aim of assessing the incidence and characteristics of diarrhea and to investigate possible associated co-factors in proton pump inhibitor users in daily practice. Data were used from a prospective, observational study in which 10,008 lansprazole users were followed over time (1994-1998). The study was designed according to the SAMM guidelines. A nested case-control design was used to compare proton pump inhibitor users reporting diarrhea with those reporting no diarrhea. The frequency of diarrhea was 3.7% and the incidence density 10.7 per 1000 patients months of proton pump inhibitor use. The diarrhea was most commonly loose and occurred on average 4.4 times per day. The analysis of co-factors revealed that patients with concomitant use of oral antibiotics and patients reporting neurological and/or dermatological adverse events, were at risk of developing diarrhea during proton pomp inhibitor use.|For more Drug Warnings (Complete) data for LANSOPRAZOLE (8 total), please visit the HSDB record page.

Lansoprazole decreases gastric acid secretion by targeting H+,K+-ATPase, which is the enzyme that catalyzes the final step in the acid secretion pathway in parietal cells. Conveniently, lansoprazole administered any time of day is able to inhibit both daytime and nocturnal acid secretion. The result is that lansoprazole is effective at healing duodenal ulcers, reduces ulcer-related pain, and offers relief from symptoms of heartburn Lansoprazole also reduces pepsin secretion, making it a useful treatment option for hypersecretory conditions such as Zollinger-Ellison syndrome.

Compounds that inhibit H(+)-K(+)-EXCHANGING ATPASE. They are used as ANTI-ULCER AGENTS and sometimes in place of HISTAMINE H2 ANTAGONISTS for GASTROESOPHAGEAL REFLUX. (See all compounds classified as Proton Pump Inhibitors.)|Various agents with different action mechanisms used to treat or ameliorate PEPTIC ULCER or irritation of the gastrointestinal tract. This has included ANTIBIOTICS to treat HELICOBACTER INFECTIONS; HISTAMINE H2 ANTAGONISTS to reduce GASTRIC ACID secretion; and ANTACIDS for symptomatic relief. (See all compounds classified as Anti-Ulcer Agents.)

The oral bioavailability of lansoprazole is reported to be 80-90% and the peak plasma concentration(Cmax) is achieved about 1.7 hours after oral dosing. Food reduces the absorption of lansoprazole (both Cmax and AUC are reduced by 50-70%); therefore, patients should be instructed to take lansoprazole before meals.|A reported 14-23% of a lansoprazole is eliminated in the urine with this percentage range including both conjugated and unconjugated hydroxylated metabolites.|The apparent volume of distribution of lansoprazole is 0.4 L/kg.|The reported clearance of lansoprazole is 400-650 mL/min.|Very high (around 97%) /protein binding/; protein binding remains constant over the concentration range of 0.05 to 5 ug/mL. In patient with renal function impairment, protein binding may be decreased by 1 to 1.5%.|Distributed in tissue, particularly gastric parietal cells. Apparent oral volume of distribution following administration of 30 mg of lansoprazole is about 0.5 L/kg.|Since lansoprazole is acid-labile, it is administered as a capsule containing enter-coated granules to prevent gastric decomposition and to increase bioavailability. Once lansoprazole has left the stomach, absorption is rapid and relatively complete, with absolute bioavailability over 80%. Bioavailability may be decreased if lansoprazole is administered within 30 minutes of food intake as compared to that of a fasting state. Absorption may be delayed in patients with hepatic cirrhosis.|Elimination: Renal: Approximately 14 to 25% of a dose of lansoprazole is excreted in the urine, as conjugated and unconjugated hydroxylated metabolites. Less than 1% of unchanged lansoprazole is detectable in the urine. Biliary/fecal: Approximately two-thirds of a dose of lansoprazole is detected as metabolites in the feces. In dialysis: Lansoprazole and its metabolites are not significantly dialyzed; no appreciable fraction is removed by hemodialysis. Note: Elimination is prolonged in healthy elderly subjects, in adult and elderly patient with mild renal impairment, and in patients with severe liver disease.|For more Absorption, Distribution and Excretion (Complete) data for LANSOPRAZOLE (6 total), please visit the HSDB record page.

Lansoprazole is predominantly metabolized in the liver by CYP3A4 and CYP2C19. The resulting major metabolites are 5-hydroxy lansoprazole and the sulfone derivative of lansoprazole.|Lansoprazole is extensively metabolized in the liver to two main excretory metabolites that are inactive. In the acidic environment of the gastric parietal cell, lansoprazole is converted to two active compounds that inhibit acid secretion by (H+,K+)-ATPase within the parietal cell canaliculus, but that are not present in the systemic circulation.

One source reports the half life of lansoprazole to be 0.9 - 1.6 hours, while another source cites 0.9 - 2.1 hours. The general consensus is that lansoprazole has a short half life and is approximately 2 hours or less. These numbers may be misleading since it suggests that lansoprazole has a short duration of action when in practice, lansoprazole can effectively inhibit acid secretion for ~24 hours due to it's mechanism of action.|Elimination: Normal renal function: Approximately 1.5 hours. Renal function impairment: Shortened elimination half-life. Elderly patients: 1.9 to 2.9 hours. Hepatic function impairment: 3.2 to 7.2 hours.

As a PPI, lansoprazole is a prodrug and requires protonation via an acidic environment to become activated. Once protonated, lansoprazole is able to react with cysteine residues, specifically Cys813 and Cys321, on parietal H+,K+-ATPase resulting in stable disulfides. PPI's in general are able to provide prolonged inhibition of acid secretion due to their ability to bind covalently to their targets.|Lansoprazole is a selective and irreversible proton pump inhibitor. In the acidic environment of the gastric parietal cell, lansoprazole is converted to active sulphenamide derivatives that bind to the sulfhydryl group of (H+, K+)-adenosine triphosphatase ((H+,K+)-ATPase), also known as the proton pump (H+,K+)-ATPase catalyzes the final step in the gastric acid secretion pathway. Lansoprazole's inhibition of (H+,K+)-ATPase results in inhibition of both centrally and peripherally mediated gastric acid secretion. The inhibitory effect is dose-related. Lansoprazole inhibits both basal and stimulated gastric acid secretion regardless of the stimulus.

/HUMAN EXPOSURE STUDIES/ In one reported case of overdose, the patient consumed 600 mg of lansoprazole with no adverse reaction.

2-(((3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl)methyl)sulfinyl)benzimidazole

Trade names: Agopton, Lansox, Lanzor, Limpidex, Ogast, Prevacid, Takepron, Zoton

Preparation: A. Nohara, Y. Maki, EP 174726; US 4628098 (both 1986 to Takeda)

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients