Dexlansoprazole

Dexlansoprazole belongs to the Gastrointestinal Agent acts as a Proton Pump Inhibitor.

Dexlansoprazole is a proton pump inhibitor used to help gastrointestinal ulcers heal, to treat symptoms of gastroesophageal reflux disease (GERD), to eradicate Helicobacter pylori, and to treat hypersecretory conditions such as Zollinger-Ellison Syndrome.

After oral administration, the peak plasma concentration increases approximately dose proportionally. The dual delayed release formulation achieves two plasma concentration peaks, where the first peak occurs one to two hours after administration, followed by a second peak within four to five hours. AUC was found to be 3275 (ng∙h/mL). The apparent volume of distribution after multiple doses in symptomatic GERD patients was 40.3 L and Plasma protein binding of dexlansoprazole ranged from 96% to 99% in healthy subjects. Extensively metabolized in the liver into inactive metabolites by CYP2C19 and CYP3A4 enzymes via hydroxylation and oxidation respectively; followed by formation of sulphate, glucuronide, and glutathione conjugates. Excretion mainly takes place approximately 51% as metabolites via urine and approximately 48% Faeces.

Dexlansoprazole shows side effects like Gas, Nausea, vomiting, diarrhoea.

Dexlansoprazole is available in the form of Oral delayed capsule.

Dexlansoprazole is available in India, US, Canada, Germany, Singapore, France, UK, Malaysia, Spain, China, and Australia.

Dexlansoprazole belongs to the Gastrointestinal Agent acts as a Proton Pump Inhibitor.

Dexlansoprazole is Proton pump inhibitor; decreases acid secretion in gastric parietal cells through inhibition of (H+, K+)-ATPase enzyme system, blocking the final step in gastric acid production.

The onset of action of Ranitidine can be observed after an hour of oral administration.

The duration of action of Ranitidine lasts for an average duration of 24 hours.

Dexlansoprazole is available in the form of Oral delayed capsule.

Dexlansoprazole delayed capsule is taken orally, usually once daily.

Dexlansoprazole is an anti-ulcer medicine used to treat conditions where the stomach produces too much acid. It is used to treat heartburn associated with non-erosive gastroesophageal reflux disease, a condition where acid from the stomach and bile irritates the food pipe. It is also used for healing the damage to the oesophagus (food pipe) due to excess acid production.

Dexlansoprazole belongs to the Gastrointestinal Agent acts as a Proton Pump Inhibitor.

Dexlansoprazole is Proton pump inhibitor; decreases acid secretion in gastric parietal cells through inhibition of (H+, K+)-ATPase enzyme system, blocking the final step in gastric acid production.

Dexlansoprazole is approved for use in the following clinical indications

• Eosinophilic esophagitis
• Gastroesophageal reflux disease, erosive or nonerosive

• Eosinophilic esophagitis

Adult Dose

Oral: 30 mg once daily for an 8-week trial.

Pediatric Dose

Healing: Children ≥12 years and Adolescents: Oral: 60 mg once daily for up to 8 weeks.

Maintenance of healing: Children ≥12 years and Adolescents: Oral: 30 mg once daily.

• Gastroesophageal reflux disease, erosive or nonerosive

Adult Dose

Oral: 30 mg once daily for 4 to 8 weeks

Pediatric Dose

Children ≥12 years and Adolescents: Oral: 30 mg once daily.

Dexlansoprazole is available in various strengths as 30 mg; 60 mg.

Dexlansoprazole is contraindicated in patients with

• Dexlansoprazole is contraindicated in patients with known hypersensitivity to any component of the formulation. Hypersensitivity and anaphylaxis have been reported with dexlansoprazole use. Acute interstitial nephritis has been reported with other proton pump inhibitors (PPIs), including lansoprazole.

• Gastric Malignancy

Symptomatic response with dexlansoprazole does not preclude the presence of gastric malignancy.

• Acute Interstitial Nephritis

Acute interstitial nephritis has been observed in patients taking PPIs including lansoprazole. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue dexlansoprazole if acute interstitial nephritis develops.

• Cyanocobalamin (vitamin B12) Deficiency

Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed.

• Clostridium Difficile Associated Diarrhea

Published observational studies suggest that PPI therapy like dexlansoprazole 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 dose and shortest duration of PPI therapy appropriate to the condition being treated.

• Bone Fracture

Several published observational studies suggest that 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). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the conditions being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines.

• Hypomagnesemia

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically.

• Concomitant Use of dexlansoprazole with Methotrexate

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients.

It is not known whether dexlansoprazole is excreted in human milk. However, lansoprazole and its metabolites are present in rat milk following the administration of lansoprazole. As many drugs are excreted in human milk, and because of the potential for tumorigenicity shown for lansoprazole in rat carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pregnancy Category B

There are no adequate and well-controlled studies with dexlansoprazole in pregnant women. There were no adverse fetal effects in animal reproduction studies of dexlansoprazole in rabbits. Because animal reproduction studies are not always predictive of human response, dexlansoprazole should be used during pregnancy only if clearly needed. A reproduction study conducted in rabbits at oral dexlansoprazole doses up to approximately nine times the maximum recommended human dexlansoprazole dose (60 mg/day) revealed no evidence of impaired fertility or harm to the fetus due to dexlansoprazole. In addition, reproduction studies performed in pregnant rats with oral lansoprazole at doses up to 40 times the recommended human lansoprazole dose and in pregnant rabbits at oral lansoprazole doses up to 16 times the recommended human lansoprazole dose revealed no evidence of impaired fertility or harm to the fetus due to lansoprazole.

Common

• Acute myocardial infarction, angina pectoris, bradycardia, cardiac arrhythmia , chest pain, deep vein thrombosis, edema, hypertension, palpitations, tachycardia, Acne vulgaris, dermatitis, erythema of skin, pruritus, skin lesion, skin rash, sunburn, urticaria, goiter, heavy menstrual bleeding, hypercalcemia, hypokalemia, increased gastrin, increased serum glucose, increased serum potassium, increased serum total protein, menstrual disease, weight gain, Abdominal distress, abdominal pain, abdominal tenderness, abnormal bowel sounds, abnormal stools, anorectal pain , Barrett esophagus, bezoar formation , biliary colic, change in appetite, cholelithiasis, colitis, colonic polyps, constipation, delayed gastric emptying, diarrhea, duodenitis, dysgeusia, dyspepsia, dysphagia, enteritis, eructation, esophagitis, flatulence, gastric polyp, gastritis, gastroenteritis, gastroesophageal reflux disease, gastrointestinal disease, gastrointestinal hypermotility, gastrointestinal perforation, gastrointestinal ulcer, halitosis, hematemesis, hematochezia, hemorrhoids , hiccups , irritable bowel syndrome, mucosal swelling , mucus stools , oral bullae , oral herpes simplex infection, oral paresthesia, proctitis, retching, sore throat, vomiting, xerostomia, Dysmenorrhea, dyspareunia , dysuria , urinary urgency, vulvovaginal infection, Anemia, decreased platelet count , lymphadenopathy, rectal hemorrhage, Decreased serum bilirubin , hepatomegaly, increased serum alanine aminotransferase , increased serum alkaline phosphatase, increased serum aspartate aminotransferase, increased serum bilirubin, Hypersensitivity reaction, Candidiasis, influenza, viral infection, Abnormal dreams, anxiety, chills, depression, dizziness, falling, feeling abnormal, headache, insomnia, memory impairment, migraine, pain, painful defecation, paresthesia, procedural pain, psychomotor agitation, seizure, trigeminal neuralgia, vertigo, Arthralgia, arthritis, asthenia, bone fracture, joint sprain, muscle cramps, musculoskeletal pain, myalgia, tremor, Eye irritation, swelling of eye, Otalgia, tinnitus, Increased serum creatinine, Asthma, bronchitis, cough, dyspnea, hyperventilation, nasopharyngitis, oropharyngeal pain (adolescents: ≥5%), pharyngitis, pulmonary aspiration, respiratory congestion, sinusitis, upper respiratory tract infection, Fever, inflammation, nodule.

Rare

• Cerebrovascular accident, hypersensitivity angiitis, transient ischemic attacks, Acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, Hypocalcemia, hypomagnesemia, hyponatremia, Clostridioides difficile associated diarrhea, pancreatitis, Chronic renal failure , Autoimmune hemolytic anemia, immune thrombocytopenia, Hepatitis, hepatotoxicity (idiosyncratic), Anaphylactic shock, Blurred vision, Deafness, Acute kidney injury, Constriction of the pharynx.

• Drugs with pH-Dependent Absorption Kinetics

Due to its effects on gastric acid secretion, dexlansoprazole can reduce the absorption of drugs where gastric pH is an important determinant of their bioavailability. Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ampicillin esters, ketoconazole, atazanavir, iron salts, erlotinib, and mycophenolate mofetil (MMF) can decrease, while the absorption of drugs such as digoxin can increase during treatment with dexlansoprazole. dexlansoprazole is likely to substantially decrease the systemic concentrations of the HIV protease inhibitor atazanavir, which is dependent upon the presence of gastric acid for absorption, and may result in a loss of therapeutic effect of atazanavir and the development of HIV resistance. Therefore, DEXLANSOPRAZOLE should not be co-administered with atazanavir. Co-administration of PPIs in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving PPIs and MMF. Use dexlansoprazole with caution in transplant patients receiving MMF.

• Warfarin

Co-administration of dexlansoprazole 90 mg and warfarin 25 mg 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 dexlansoprazole and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.

• Tacrolimus

Concomitant administration of dexlansoprazole and tacrolimus may increase whole blood levels of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19.

• Clopidogrel

Concomitant administration of dexlansoprazole 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 dexlansoprazole.

• Methotrexate

Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of high-dose methotrexate with PPIs have been conducted.

The common side effects of Dexlansoprazole include the following

Common side effects

• Gas, Nausea, vomiting, diarrhea.

Rare side effects

• Blistering, peeling, or bleeding skin, sores on the lips, nose, mouth, or genitals, swollen glands, shortness of breath; fever; or flu-like symptoms, rash, hives, itching, swelling of the eyes, face, lips, mouth, throat, or tongue, difficulty breathing or swallowing, or hoarseness, irregular, fast, or pounding heartbeat; muscle spasms; uncontrollable shaking of a part of the body, excessive tiredness, lightheadedness, dizziness, or seizures, severe diarrhea with watery stools, stomach pain, increased or decreased urination, blood in urine, fatigue, nausea, loss of appetite, fever, rash, or joint pain.

• Pregnancy

Pregnancy Category B

There are no adequate and well-controlled studies with dexlansoprazole in pregnant women. There were no adverse fetal effects in animal reproduction studies of dexlansoprazole in rabbits. Because animal reproduction studies are not always predictive of human response, dexlansoprazole should be used during pregnancy only if clearly needed. A reproduction study conducted in rabbits at oral dexlansoprazole doses up to approximately nine times the maximum recommended human dexlansoprazole dose (60 mg/day) revealed no evidence of impaired fertility or harm to the fetus due to dexlansoprazole. In addition, reproduction studies performed in pregnant rats with oral lansoprazole at doses up to 40 times the recommended human lansoprazole dose and in pregnant rabbits at oral lansoprazole doses up to 16 times the recommended human lansoprazole dose revealed no evidence of impaired fertility or harm to the fetus due to lansoprazole.

• Nursing Mothers

It is not known whether dexlansoprazole is excreted in human milk. However, lansoprazole and its metabolites are present in rat milk following the administration of lansoprazole. As many drugs are excreted in human milk, and because of the potential for tumorigenicity shown for lansoprazole in rat carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

• Pediatric Use

Safety and effectiveness of dexlansoprazole in pediatric patients (less than 18 years of age) have not been established.

• Geriatric Use

In clinical studies of dexlansoprazole, 11% of patients were aged 65 years and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified significant differences in responses between geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Symptoms: Hypertension, hot flashes, contusion, oropharyngeal pain, weight loss.

Management: Symptomatic and supportive treatment.

Pharmacodynamic

Dexlansoprazole is a proton pump inhibitor (PPI) and is included in the drug class of antisecretory compounds. It blocks the final step of gastric acid secretion by specific inhibition of the (H+, K+)-ATPase at the secretory surface of the parietal cells on gastric mucosa.

Pharmacokinetics

• Absorption

After oral administration, the peak plasma concentration increases approximately dose proportionally. The dual delayed release formulation achieves two plasma concentration peaks, where the first peak occurs one to two hours after administration, followed by a second peak within four to five hours. AUC was found to be 3275 (ng∙h/mL).

• Distribution

The apparent volume of distribution after multiple doses in symptomatic GERD patients was 40.3 L and Plasma protein binding of dexlansoprazole ranged from 96% to 99% in healthy subjects.

• Metabolism and Excretion

Extensively metabolized in the liver into inactive metabolites by CYP2C19 and CYP3A4 enzymes via hydroxylation and oxidation respectively; followed by formation of sulphate, glucuronide, and glutathione conjugates. Excretion mainly takes place approximately 51% as metabolites via urine and approximately 48% Faeces.

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