A. GER is the passage of gastric contents into the esophagus, with or without regurgitation and vomiting. GER is a normal physiologic process occurring several times per day in healthy infants, children and adults. Most episodes of GER in healthy individuals last <3 minutes, occur in the postprandial period, and cause few or no symptoms. GERD (gastroesophageal reflux disease) refers to the symptoms or complications that may occur when gastric contents reflux into the esophagus or oropharynx.

A. In a great majority of infants, reflux is physiologic and most outgrow it by 1 to 2 years of age. In a community-based study of healthy and thriving infants, GER occurred in 67% of infants around the age of 4 to 5 months, declining rapidly to 21 % by the age of 6 to 7 months and to less than 5% by 12 months.¹

In a large Indian study from Delhi, a prevalence of 10% was observed among children in the age group of 1 month to 2 years.²

A. Prevalence of GERD in children is not well-defined, but community-based studies suggest that symptoms may be present in 1.8 to 22% of children, aged 3 to 18 years.¹ GERD is present in a high proportion (31.3%) in children with cerebral palsy.³

A. The prevalence of GERD is increasing day by day due to various reasons such as changing food habits of children (spicy and fatty foods, caffeine, chocolates, carbonated beverages, etc.), increasing obesity, stress in schools, tight clothing, and exposure to tobacco smoke, etc.

A. Studies have suggested that 60-80% of childhood asthmatic patients experience GERD.⁴

A. The predisposed conditions for developing severe-chronic GERD in children are neurologic impairment, obesity, repaired esophageal atresia or any other congenital esophageal disease, cystic fibrosis, hiatal hernia, repaired achalasia, lung transplant, and a family history of GERD.⁵

A. GERD diagnosis is based on history and clinical features. Clinical presentation of infants and children with GERD may be different. Esophageal symptoms are as follows:

Some children with GERD may complain of extra-esophageal symptoms like cough at night, hoarseness of voice, wheezing, recurrent laryngitis, recurrent sinusitis, recurrent otitis media, dental erosion, etc.

A. The following cases can be suspected as GERD-related asthma:⁶

A. Investigations of proven usefulness available for the diagnosis of GERD are as follows:

In India, facilities for pH monitoring are available at very few centers. However, endoscopy can be done in almost all major cities. Esophageal pH monitoring has a special place in the diagnosis and management of endoscopy-negative GERD, non-erosive esophagitis, persistent asthma or pulmonary problems with suspected GER, and in those who do not respond to treatment with acid suppressants. Barium contrast radiography is useful to confirm or rule out anatomic abnormalities of the upper gastrointestinal (Gl) tract. Nuclear scintigraphy provides information about gastric emptying, which may be delayed in children with GERD.

A. Indications for investigating the patient are as below:

A. The symptom complexes that need initiation of treatment are as follows:

A. The treatment goals are

Frequency and duration of GERD are direct predictors of long-term GERD complications in adults.⁷ Hence, intervention in childhood GERD results in a better disease outcome when they are adults.⁸

A. Pharmacological intervention is often necessary to relieve the reflux symptoms and to promote healing of the injury in the esophagus. Various groups of drugs used are antacids, prokinetics, histamine₂-receptor antagonists (H₂RAs) and proton pump inhibitors (PPIs). Antacids neutralize the gastric acid, but there is concern about side effects; the need for more than 6 doses per day and availability of better options has limited their regular use. Prokinetics increase the tone of the LES to prevent reflux whereas H₂RAs and PPIs suppress the acid secretion from parietal cells. Commonly prescribed prokinetics are metoclopramide, domperidone and erythromycin. There is no clear scientific evidence that any of them greatly improve the condition.

As shown in the figure, H₂RAs act by blocking only the H₂-receptors whereas PPIs act at the final step of acid production and, overall, provide a more potent inhibition of the acid secretion.

A. PPIs are more potent acid suppressors than H₂RAs.⁸

A. Lansoprazole, omeprazole and esomeprazole have been approved forthe use of GERD in children. Lansoprazole and esomeprazole should be used in children ≥ 1 year of age and omeprazole for those ≥ 2 years of age.

A. Surgical treatment needs to be considered in the following conditions:

In a multicenter, open-label study, 66 children with symptomatic GERD and erosive esophagitis (diagnosed on endoscopy) were enrolled. Patients were assigned to lansoprazole 15 mg (≤ 30 kg) or 30 mg (>30 kg) once daily for 8 to 12 weeks.

Frequency and daily severity of symptoms, and the frequency and quantity of antacid used were reduced significantly compared to baseline from the second week of treatment.

Among children with erosive esophagitis (EE), lesions got healed up to 78% by week 8 and 100% by week 12.

Resolution of cough and wheeze occurred in 79% and 63% of children with GERD, respectively.

92% of children were highly compliant.

GERD symptoms resolved or improved compared to baseline in 76% of children with 12 weeks of lansoprazole treatment. Repeat endoscopy conducted at 12 weeks demonstrated healing in all children with erosive esophagitis. Lansoprazole once daily is effective in healing EE and in relieving GERD-related symptoms in children aged 1 to 11 years.

In an open-label, multicenter study, 64 adolescents (aged 12 to 17 years) with symptomatic GERD and 23 adolescents with erosive esophagitis (diagnosed on endoscopy) were enrolled. Patients of symptomatic GERD were given lansoprazole 15 mg once daily for 8 weeks and those with erosive esophagitis were given lansoprazole 30 mg once daily for 8 to 12 weeks.

Of all the adolescents, 74% exhibited symptom resolution and improvement at the end of the study.

Frequency and daily severity of symptoms, and the frequency and quantity of antacid used were reduced significantly compared to baseline with 8 weeks of treatment.

95% of the adolescents with EE had endoscopy confirmed mucosal healing by 8 weeks.

Lansoprazole is well-tolerated and is effective in reducing gastroesophageal symptoms in adolescents with non-erosive GERD and erosive esophagitis, and in healing erosive esophagitis.

This is a retrospective observational study, which used data from 1999 to 2004. The objective was to examine the use of PPIs in infants and neonates.

Of 1,308,126 infants younger than 12 months in the claims database, a total of 2469 infants received PPI therapy during the study period. Prevalence of PPI use in infants increased 7.5 fold from 1999 to 2004 and 4-fold from 1999 to 2003.

Before 2003, omeprazole accounted for the majority of the claims for PPIs. During 2003 and 2004, lansoprazole was used more than omeprazole among infants and, overall, the prevalence of PPI use continued to rise. The use of PPIs other than lansoprazole and omeprazole was uniformly rare (1 -2%).

The most common diagnosis was GER (59%), feeding problems (23%), upper respiratory infection (23%), esophagitis (21 %) and pain from gas (20%). Pre-index H₂ blockade was evident in 58% of the patients; pre-index metoclopramide was used in 38% of the patients.

The median daily dose of lansoprazole was 1.74 mg/kg/day.

Pediatric gastroenterology and general pediatrics accounted for nearly 87%.

The 'typical' course of PPIs lasted 1 to 3 months, with a mean age at index of 4 to 5 months and a mean age discontinuation of 7 to 8 months.

In a multicenter, open-label study, 30 consecutive infants (aged 3 to 7 months) with GERD, whose conditions were diagnosed by the Infant Gastroesophageal Reflux Questionnaire scores (l-GERD) of ≥ 16, were randomly assigned to receive one of two lansoprazole dosing regimens: 15 mg given once per day (Group A) or approximately 7.5 mg given two times per day (Group B). Matched infants in a control group were treated with an extensively hydrolyzed formula (Group C). Daily l-GERD-R scores were gathered and the scores after 1 and 2 weeks of treatment were used for analysis.

At the end of 2 weeks of treatment, similar number of patients in Group A (60%) and Group B (67%) demonstrated a significant reduction in their scores, and this was higher than in Group C (20%).

Overall, there was no difference in the symptom response in both groups, but the twice-daily regimen produced a faster symptom response.

Changing the dosing regimen of lansoprazole on the basis of age may be important for achieving the greatest efficacy.

Lansoprazole is generally well tolerated.

In studies, 15% of children experienced side effects, which were mild to moderate in nature. These usually involved Gl events (nausea, vomiting, diarrhea, constipation) and headache.

No clinically significant changes in hematological and biochemical parameters were found.

In a multicenter, open-label study, 113 children (59 male; median age: 4.5 years) receiving PPI therapy continuously for 1 year or more, with baseline and follow-up esophageal and gastric biopsies, were enrolled. The median treatment duration was 35.2 months.

Lansoprazole was the most frequently prescribed PPI (65% of children).

Overall, 88% (99/113) of children had no adverse events during the PPI treatment. For the 12% with at least one adverse event, the most frequent were diarrhea (5%) and constipation (4%).

The results of this retrospective analysis suggest that continuous long-term PPI therapy in pediatric patients is safe.

A. Lansoprazole is available in capsule, ODT (orally disintegrating tablet) and oral suspension forms. Each packet of delayed-release oral suspension contains enteric-coated granules.

A. This is a new, patient-friendly and more convenient formulation of lansoprazole, which can be taken with or without water. It represents an innovative drug delivery system, comprising enteric-coated microgranules of the drug with an inactive rapidly dispersing matrix to form a tablet. When the tablet is placed on the tongue and sucked gently, it disintegrates rapidly in the mouth, releasing the enteric-coated microgranules, which are swallowed with the patient's saliva, without needing water. Alternatively, an ODT can be first dispersed in water in a spoon or a syringe and then given to the patient.

Lansoprazole ODT has been shown to have a similar bioavailability as the capsules.

A. The size of each microgranule is 400-500 microns. Each microgranule has four layers. The active lansoprazole layer surrounds an inert core, followed by two inert under-coating layers of HPMC (Hydroxy Propyl Methyl Cellulose). The outermost layer is an enteric coating, which prevents the dissolution of lansoprazole in the stomach, improves stability, reduces damage during compression and neutralizes the taste of the microgranule.

A. The advantages of an ODT are as follows:

A. The bioavailability of lansoprazole ODT is as below:

A. A study involving general practitioners (GPs) in the U.K. recruited 156 adu given lansoprazole ODTs. After questioning them,

A. A study was conducted in Italy through telephone interviews with 100 GPs, 150 gastroenterologists, 20 oncologists, 20 rheumatologists and 20 cardiologists.

Lansoprazole ODT was prescribed for all patients, with 84% of prescriptions receiving a PPI for the first time.

When asked to describe the formulation, they stressed on the rapidity of action, good efficacy and the ease of administration.

A. Lansoprazole is available in sachets in the form of granules with some solution-forming component. When the sachet is opened and the contents poured in water, the solution-forming component gets dissolved whereas the lansoprazole granules remain suspended. This forms the oral suspension.

A. JUNIOR LANZOL is available as ODTs of lansoprazole in two strengths, 15 mg and 30 mg, and are available as blister packs of 10 tablets. It is also available as 15 mg granules in sachets to make an oral suspension. It has been specially developed in a strawberry flavor, keeping in mind the need of pediatric patients with GERD.

A. JUNIOR LANZOL is used for the short-term treatment of symptomatic GERD in children, 1 to 11 years of age. The dosage is as follows:

The dose can be increased up to 30 mg b.i.d. if patients remain symptomatic even after 2 or more weeks of treatment.

A. For the age group of 12 to 17 years, the dosage is as follows:

A. The methods of administration of JUNIOR LANZOL ODT are as follows:

A. The mode of administration of JUNIOR LANZOL for Oral Suspension (Granules) is as follows:

A. Lansoprazole is metabolized through the cytochrome P₄₅₀ (CYP 450) 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 CYP450 system, such as warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propranolol, prednisone, diazepam or clarithromycin in healthy subjects. Lansoprazole has also been shown to have no clinically significant interaction with amoxicillin.

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 is unlikely to be of clinical concern. Nonetheless, individual patients may require additional titration of their theophylline dosage when lansoprazole is started or stopped to ensure clinically effective blood levels.

Each uncoated tablet contains:
Lansoprazole USP................15 mg (as enteric-coated pellets)
Colours: Titanium Dioxide & Red Oxide of Iron

Each uncoated tablet contains:
Lansoprazole USP................30 mg (as enteric-coated pellets)
Colours: Titanium Dioxide & Red Oxide of Iron

Each sachet contains:
Lansoprazole USP................15 mg (as enteric-coated pellets)
Colour: Red Oxide of Iron

Orally disintegrating tablets (ODT) and granules for oral suspension.

Lansoprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, 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 the inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. Lansoprazole does not exhibit anticholinergic or histamine type-2 antagonist activity.

After oral administration, lansoprazole was shown to significantly decrease the basal acid output and significantly increase the mean gastric pH and the percentage of time during which the gastric pH was >3 and >4. Lansoprazole also significantly reduced meal-stimulated gastric acid output and secretion volume, as well as pentagastrin-stimulated acid output. In patients with hypersecretion of acid, lansoprazole significantly reduced basal and pentagastrin-stimulated gastric acid secretion. Lansoprazole inhibited the normal increases in secretion volume, acidity and acid output induced by insulin.

Lansoprazole ODTs and lansoprazole for oral suspension contain enteric-coated granules of lansoprazole.

Absorption is rapid, with mean peak plasma levels of lansoprazole occurring after approximately 1.7 hours. After a single-dose administration of 15 mg to 60 mg of oral lansoprazole, the peak plasma concentrations (C_max) of lansoprazole and the area under the plasma concentration curves (AUCs) of lansoprazole were approximately proportional to the administered dose. Lansoprazole does not accumulate and its pharmacokinetics is unaltered by multiple dosing. Overall, lansoprazole pharmacokinetics in pediatric patients, aged 1 to 17 years, is similar to that observed in healthy adult subjects.

The absorption of lansoprazole is rapid, with mean C_max occurring approximately 1.7 hours after oral dosing and the absolute bioavailability over 80%. The mean (±SD) plasma half-life was 1.5 (±1.0) hours. Both the C_max and the AUC are diminished by about 50-70% if lansoprazole is given 30 minutes after food, compared to the fasting condition. There is no significant food effect if lansoprazole is given before meals.

Lansoprazole is 97% bound to plasma proteins. Plasma protein-binding is constant over the concentration range of 0.05 to 5.0 μg/mL

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 blocking the proton pump [(H⁺, K⁺)-ATPase enzyme system] at the secretory surface of the gastric parietal cell. The two active species are not present in the systemic circulation. The plasma elimination half-life of lansoprazole is less than 2 hours while the acid inhibitory effect lasts more than 24 hours. Therefore, the plasma elimination half-life of lansoprazole does not reflect its duration of suppression of gastric acid secretion.

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.

JUNIOR LANZOL ODTs/for Oral Suspension should be given 30 minutes before meals.

JUNIOR LANZOL ODTs 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 who have difficulty doing so, Junior Lanzol 15/30 ODTs can be administered in the following ways:

It can be administered with a spoon as follows:

Place a 15 mg tablet in a teaspoon containing approximately 4 ml of water, or place two 15 mg tablets or one 30 mg tablet in a tablespoon containing approximately 10 ml of water.

Wait till the tablet/tablets get disintegrated.

Administer the contents.

Refill the spoon with water and administer any remaining contents.

For hospitalized patients who cannot take lansoprazole orally, it can be administered via a nasogastric tube as follows:

Place a 15 mg tablet in a syringe and draw up 4 ml of water, or place two 15 mg tablets or one 30 mg tablet in a syringe and draw up 10 ml of water.

Shake gently to allow for quick disintegration.

After the tablet has disintegrated, inject through the nasogastric tube into the stomach within 15 minutes.

Refill the syringe with approximately 5 ml of water, shake gently, and flush the nasogastric tube.

Should be administered as follows:

Open the packet

To prepare a dose, empty the packet contents into a container having two tablespoons (30 ml) of water. DO NOT USE OTHER LIQUIDS OR FOODS.

Stir well and drink immediately.

If any material remains after drinking, add more water, stir, and drink immediately.

This product should not be given through enteral administration tubes (Ryles Tube).

Lansoprazole is contraindicated in patients with known severe hypersensitivity to any component of the formulation of lansoprazole.

The safety and effectiveness of lansoprazole has been established in pediatric patients, aged 1 to 17 years, for the short-term treatment of symptomatic and erosive esophagitis. Use of lansoprazole in this population is supported by evidence from adequate and well-controlled studies of lansoprazole in adults, with additional clinical, pharmacokinetic, and pharmacodynamic studies performed in pediatric patients. The adverse events profile in pediatric patients is similar to that of adults. There were no adverse events reported in clinical studies that were not previously observed in adults. However, lansoprazole is not effective in symptomatic GERD patients of 1 month to less than 1 year of age in a multicenter, double-blind, placebo-controlled study.

Lansoprazole is metabolized through the cytochrome P₄₅₀ (CYP 450) 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 CYP450 system, such as warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propranolol, prednisone, diazepam, or clarithromycin in healthy subjects. These compounds are metabolized through various CYP450 isozymes, including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A.

Drugs with pH-Dependent Absorption Kinetics: It is theoretically possible that lansoprazole and other proton pump inhibitors (PPIs) may interfere with the absorption of other drugs where gastric pH is an important determinant of oral bioavailability (e.g., ampicillin esters, digoxin, iron salts, ketoconazole).

Atazanavir: Lansoprazole causes long-lasting inhibition of gastric acid secretion. Lansoprazole substantially decreases 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 the therapeutic effect of atazanavir and the development of HIV resistance. Therefore, lansoprazole, or other PPIs, should not be co-administered with atazanavir.

Warfarin: In a study of healthy subjects, neither the pharmacokinetics of warfarin enantiomers nor the prothrombin time were affected following single or multiple 60 mg doses of lansoprazole. However, there have been reports of an increased International Normalized Ratio (INR) and prothrombin time in patients receiving PPIs, including lansoprazole and warfarin, concomitantly. Increases in the INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with PPIs and warfarin concomitantly may need to be monitored for increases in the INR and prothrombin time.

Theophylline: 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 is unlikely to be of clinical concern. Nonetheless, individual patients may require additional titration of their theophylline dosage when lansoprazole is started or stopped to ensure clinically effective blood levels. Although the magnitude of the effect on theophylline clearance is small, individual patients may require additional titration of their theophylline dosage when lansoprazole is started or stopped to ensure clinically effective blood levels.

Methotrexate and 7-hydromethotrexate: In an open-label, single-arm, 8-day, pharmacokinetic study of 28 adult rheumatoid arthritis patients (who required the chronic use of 7.5 to 15 mg of methotrexate given weekly), administration of 7 days of naproxen 500 mg twice daily and lansoprazole 30 mg daily had no effect on the pharmacokinetics of methotrexate and 7-hydroxymethotrexate. While this study was not designed to assess the safety of this combination of drugs, no major adverse reactions were noted.

Amoxicillin: Lansoprazole has also been shown to have no clinically significant interaction with amoxicillin.

Sucralfate: In a single-dose crossover study examining lansoprazole 30 mg and omeprazole 20 mg, each administered alone and concomitantly with sucralfate 1 g, absorption of the PPIs was delayed and their bioavailability was reduced by 17% and 16%, respectively, when administered concomitantly with sucralfate. Therefore, PPIs should be taken at least 30 minutes prior to sucralfate. In clinical trials, antacids were administered concomitantly with lansoprazole and there was no evidence of a change in the efficacy of lansoprazole.

Renal impairment is not expected to after PPI elimination, since little unchanged parent drug is excreted in the urine; the kidneys are responsible for most of the excretion of inactive PPI metabolites. No dosage adjustment appears necessary for patients with renal impairment. The pharmacokinetics of lansoprazole in patients with various degrees of renal impairment was not substantially different compared to those in subjects with normal renal function.

In patients with various degrees of chronic hepatic impairment, an increase in the mean AUC of up to 500% was observed at the steady state compared to healthy subjects. Consider dose adjustment in patients with severe hepatic impairment. In adults with hepatic impairment, reduced clearance of PPIs was observed. In such patients, the dosage of PPIs should be reduced by 50%. Although similar findings are expected in the pediatric population, the impact of liver dysfunction on PPI disposition in children has never been studied.

There are no adequate or well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Animal studies indicate that lansoprazole is secreted into breast milk. There is no information on the secretion of lansoprazole into breast milk in humans. However, breastfeeding should be discontinued if the use of lansoprazole is considered essential.

Lansoprazole 15-30 mg once daily was generally well tolerated in children and adolescents in clinical trials. Treatment-related adverse events were experienced by 15% of children and adolescents treated for 8 to 12 weeks. The majority of adverse events were mild to moderate in severity. Most frequent adverse events were headache, constipation, and abdominal pain. There were no clinically significant changes in hematological and biochemical parameters.

Oral doses up to 5000 mg/kg in rats (approximately 1300 times the recommended human dose based on body surface area) and in 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.

JUNIOR LANZOL 15/30 ODTs
Store in a cool, dry place. Protect from light.

JUNIOR LANZOL Granules for Oral Suspension 15 mg
Store in a cool, dry place. Protect from light.

JUNIOR LANZOL 15/30 ODTs
Blister pack of 10 tablets

JUNIOR LANZOL for Oral Suspension
Unit dose carton of 20 sachets