JUNIOR LANZOL ODT

Lansoprazole

Prescribing information

Composition

JUNIOR LANZOL 15

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

JUNIOR LANZOL 30

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

Lansoprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, which 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. Lansoprazole does not exhibit anticholinergic or histamine type-2 antagonist activity.

Antisecretory Activity

After oral administration, lansoprazole was shown to significantly decrease the basal acid output and significantly increase the mean gastric pH and percent of time 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.

Pharmacokinetics

Lansoprazole ODT contains enteric-coated pellets of lansoprazole.

Absorption begins only after the granules leave the stomach. 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.

The pharmacokinetics of lansoprazole was studied in paediatric patients (aged 1 to 11 years and 12 to 17 years) with gastroesophageal reflux disease (GERD) in two separate clinical studies. In the children aged 1 to 11 years, lansoprazole was dosed 15 mg daily for subjects weighing ≤30 kg and 30 mg daily for subjects weighing greater than 30 kg. Mean C_max and AUC values observed on day 5 of dosing were similar between the two dose groups and were not affected by weight or age within each weight-adjusted dose group used in the study. In adolescent subjects aged 12 to 17 years, subjects were randomized to receive lansoprazole at 15 mg or 30 mg daily. Mean C_max and AUC values of lansoprazole were not affected by body weight or age; also, nearly dose-proportional increases in mean C_max and AUC values were observed between the two dose groups in the study.

Overall, lansoprazole pharmacokinetics in paediatric patients aged 1 to 17 years was similar to those observed in healthy adult subjects, as described below.

Absorption

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 C_maxand AUC are diminished by about 50% to 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.

According to a study, the bioavailability of lansoprazole ODT 15 mg and 30 mg were shown to be equivalent to lansoprazole 15 mg and 30 mg capsules.

Distribution

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

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 faeces. This implies a significant biliary excretion of the metabolites of lansoprazole.

The safety and effectiveness of lansoprazole has been established in paediatric patients 1 to 17 years of age for the short-term treatment of symptomatic GERD and erosive oesophagitis; however, lansoprazole was not effective in patients with symptomatic GERD 1 month to less than 1 year of age in a multicenter, double-blind, placebo-controlled study.

Indications

Paediatric

Short-term treatment of symptomatic GERD
Short-term treatment of erosive esophagitis

Adults

Short-term treatment of active duodenal ulcer
Maintenance of healed duodenal ulcers
H. pylori eradication to reduce the risk of duodenal ulcer recurrence
Short-term treatment of active benign gastric ulcer
Healing of non-steroidal anti-inflammatory drug (NSAID)-associated gastric ulcer
Risk reduction of NSAID-associated gastric ulcer
Gastroesophageal Reflux Disease (GERD)
- Short-term treatment of symptomatic GERD
- Short-term treatment of erosive esophagitis
Maintenance of healing of erosive esophagitis
Pathological hypersecretory conditions including Zollinger-Ellison syndrome (ZES)

Dosage and Administration

Dosage

Paediatric

Indications	Recommended Dosage and Age of Paediatric Patients		Duration of Therapy
	1 to 11 years	12 to 17 years
Short-term treatment of erosive esophagitis	≤30 kg, 15 mg >30 kg, 30 mg		Once daily for up to 12 weeks⁺
Short-term treatment of symptomatic GERD	≤30 kg, 15 mg >30 kg, 30 mg		Once daily for up to 12 weeks⁺
Non-erosive GERD		15 mg	Once daily for up to 8 weeks
Erosive esophagitis		30 mg	Once daily for up to 8 weeks
Maintenance of healing of erosive esophagitis		15 mg	Once daily^#
_{+ JUNIOR LANZOL dose can be increased up to 30 mg twice daily in some paediatric patients after 2 or more weeks of treatment if they remained symptomatic.} _{# Controlled studies did not extend beyond 12 months}

Adults

Indication	Recommended Dose	Duration of Therapy
Duodenal Ulcers
Short-term treatment	15 mg	Once daily for 4 weeks
Maintenance of healed	15 mg	Once daily
*H. pylori* Eradication to Reduce the Risk of Duodenal Ulcer Recurrence*
Triple Therapy:
Lanosprazole	30 mg	Twice daily (q12h) for 10 or 14 days
Amoxicillin	1 gram	Twice daily (q12h) for 10 or 14 days
Clarithromycin	500 mg	Twice daily (q12h) for 10 or 14 days
Dual Therapy:
Lanosprazole	30 mg	Three times daily (q8h) for 14 days
Amoxicillin	1 gram	Three times daily (q8h) for 14 days
Benign Gastric Ulcer
Short-term treatment	30 mg	Once daily for up to 8 weeks
NSAID-associated Gastric Ulcer
Healing	30 mg	Once daily for 8 weeks^†
Risk reduction	15 mg	Once daily for up to 12 weeks^†
Gastroesophageal Reflux Disease (GERD)
Short-term treatment of symptomatic GERD	15 mg	Once daily for up to 8 weeks
Short-term treatment of erosive esophagitis	30 mg	Once daily for up to 8 weeks^‡
Maintenance of Healing of Erosive esophagitis	15 mg	Once daily^#
Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome	60 mg	Once daily^¶
_{* Please refer to amoxicillin and clarithromycin full prescribing information for CONTRAINDICATIONS and WARNINGS, and for information regarding dosing in elderly and renally impaired patients.} _{† Controlled studies did not extend beyond the indicated duration.} _{‡ For patients who do not heal with JUNIOR LANZOL for 8 weeks (5% to 10%), it may be helpful to give an additional 8 weeks of treatment. If there is a recurrence of erosive esophagitis, an additional 8 week course of JUNIOR LANZOL may be considered.} _{¶ Varies with individual patient. Recommended adult starting dose is 60 mg once daily. Doses should be adjusted to individual patient needs and should continue for as long as clinically indicated. Dosages up to 90 mg twice daily have been administered. Daily dose of greater than 120 mg should be administered in divided doses. Some patients with Zollinger-Ellison Syndrome have been treated continuously with JUNIOR LANZOL for more than 4 years.} _{# Controlled studies did not extend beyond 12 months}

Patients should be instructed that if a dose is missed, it should be taken as soon as possible. However, if the next scheduled dose is due, the patient should not take the missed dose, and should be instructed to take the next dose on time. Patients should be instructed not to take 2 doses at one time to make up for a missed dose.

Administration

JUNIOR LANZOL should be given 30 minutes before meals.

JUNIOR LANZOL 15/30 (orally disintegrating tablets):

JUNIOR LANZOL orally disintegrating tablets should not be broken or cut.
JUNIOR LANZOL orally disintegrating tablets 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 doing so, JUNIOR LANZOL 15/ 30 (orally disintegrating tablets) can be administered in the following ways:

JUNIOR LANZOL - Spoon

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 within 15 minutes.
Refill the spoon with water and administer any remaining contents.

JUNIOR LANZOL - Oral Syringe

It can be administered via oral syringe as follows:

Place a 15 mg tablet in oral syringe and draw up 4 ml of water, or place a 30 mg tablet in oral syringe and draw up 10 ml of water.
Shake gently to allow for a quick dispersal.
After the tablet has dispersed, administer the contents within 15 minutes.
Refill the syringe with approximately 2 ml (5 ml for the 30 mg tablet) of water, shake gently, and administer any remaining contents.

JUNIOR LANZOL - Nasogastric Tube (≥8 French) Administration

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.

USE IN OTHER FOODS AND LIQUIDS HAS NOT BEEN STUDIED CLINICALLY AND IS THEREFORE NOT RECOMMENDED.

Contraindications

Lansoprazole is contraindicated in patients with a known, severe hypersensitivity to any component of the formulation of lansoprazole. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria.

Warnings and Precautions

General

Gastric Malignancy

Symptomatic response to therapy with lansoprazole 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 lansoprazole if acute interstitial nephritis develops [see CONTRAINDICATIONS].

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 proton pump inhibitor (PPI) therapy like lansoprazole may be associated with an increased risk of Clostridium difficile associated diarrhea (CDAD), 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.

CDAD has been reported with use of nearly all antibacterial agents. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with lansoprazole, refer to WARNINGS and PRECAUTIONS sections of those package insert.

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 condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines.

Hypomagnesaemia

Hypomagnesaemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least 3 months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias and seizures. In most patients, treatment of hypomagnesaemia 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 hypomagnesaemia (e.g. diuretics), healthcare professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically.

Concomitant Use 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.

Cutaneous and Systemic Lupus Erythematosus

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including lansoprazole. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematosus cases were CLE.

The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement.

Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported.

Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving lansoprazole, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in four to 12 weeks. Serological testing (e.g., ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations.

Drug Interactions

Lansoprazole is metabolized through the cytochrome (CY) 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 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

Due to its effects on gastric acid secretion, lansoprazole 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, nelfinavir, iron salts, erlotinib, and mycophenolate mofetil (MMF) can decrease, while the absorption of drugs such as digoxin can increase during treatment with lansoprazole.

Lansoprazole is likely to substantially decrease the systemic concentrations of the HIV protease inhibitor atazanavir and nelfinavir, which are dependent upon the presence of gastric acid for absorption, and may result in a loss of therapeutic effect of atazanavir or nelfinavir and the development of HIV resistance. Therefore, lansoprazole should not be co-administered with atazanavir or nelfinavir.

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 lansoprazole with caution in transplant patients receiving MMF.

Warfarin

In a study of healthy subjects, co-administration of single or multiple 60 mg doses of lansoprazole and warfarin did not affect the pharmacokinetics of warfarin nor prothrombin time. However, there have been reports of increased International Normalized Ratio (INR) and prothrombin time in patients receiving PPIs, including lansoprazole, and warfarin, concomitantly. Increases in 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.

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.

Theophylline

When lansoprazole was administered concomitantly with theophylline (CYP1A2, CYP3A), a minor increase (10%) in the clearance of theophylline was seen. 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.

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.

Methotrexate

Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high doses; 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.

In a study of rheumatoid arthritis patients receiving low-dose methotrexate, lansoprazole and naproxen, no effect on the pharmacokinetics of methotrexate was observed.

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.

Combination Therapy with Clarithromycin

Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions due to drug interactions [see Warnings and Precautions in prescribing information for clarithromycin]. Because of these drug interactions, clarithromycin is contraindicated for co-administration with certain drugs [see Contraindications in prescribing information for clarithromycin].

For information about drug interactions of antibacterial agents (amoxicillin and clarithromycin) indicated in combination with lansoprazole, refer to the DRUG INTERACTIONS section of their package inserts.

Renal Impairment

Renal impairment is not expected to alter 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.

Hepatic Impairment

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 reduction in patients with severe hepatic impairment. In adults with hepatic impairment, reduced clearance of PPIs was observed. In such patients, the dosage of PPI should be reduced by 50%. Although similar findings are expected in the paediatric population, the impact of liver dysfunction on PPI disposition in children has never been studied.

Pregnancy

Pregnancy Category B

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.

Lactation

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.

Geriatric Use

No dosage adjustment of lansoprazole is necessary in geriatric patients. The incidence rates of lansoprazole-associated adverse reactions and laboratory test abnormalities are similar to those seen in younger patients.

Undesirable Effects

Clinical

Worldwide, over 10,000 patients have been treated with lansoprazole in Phase 2 or Phase 3 clinical trials involving various dosages and durations of treatment. In general, lansoprazole treatment has been well tolerated in both short-term and long-term trials.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The following adverse reactions were reported by the treating physician to have a possible or probable relationship to the drug in 1% or more of lansoprazole-treated patients and occurred at a greater rate in lansoprazole-treated patients than placebo-treated patients.

Table 1: Incidence of possibly or probably treatment-related adverse reactions in short-term, placebo-controlled lansoprazole studies

Body System/Adverse

Event

Lansoprazole

(n = 2768)

Placebo

(n = 1023)

Body as a Whole

Abdominal pain

2.1

1.2

Digestive System

Constipation

Diarrhoea

Nausea

1.0

3.8

1.3

0.4

2.3

1.2

Headache was also seen at greater than 1% incidence but was more common on placebo. The incidence of diarrhoea was similar between patients who received placebo and patients who received 15 mg and 30 mg of lansoprazole, but higher in the patients who received 60 mg of lansoprazole (2.9%, 1.4%, 4.2% and 7.4%, respectively).

The most commonly reported possibly or probably treatment-related adverse event during maintenance therapy was diarrhoea.

In the risk reduction study of lansoprazole for NSAID-associated gastric ulcers, the incidence of diarrhoea for patients treated with lansoprazole, misoprostol and placebo was 5%, 22% and 3%, respectively.

Another study for the same indication, where patients took either a COX-2 inhibitor or lansoprazole and naproxen, demonstrated that the safety profile was similar to the prior study. Additional reactions from this study not previously observed in other clinical trials with lansoprazole included contusion, duodenitis, epigastric discomfort, esophageal disorder, fatigue, hunger, hiatal hernia, hoarseness, impaired gastric emptying, metaplasia, and renal impairment.

Additional adverse experiences occurring in less than 1% of patients or subjects who received lansoprazole in domestic trials are shown below:

Body as a Whole: Abdomen enlarged, allergic reaction, asthenia, back pain, candidiasis, carcinoma, chest pain (not otherwise specified), chills, edema, fever, flu syndrome, halitosis, infection (not otherwise specified), malaise, neck pain, neck rigidity, pain, pelvic pain.

Cardiovascular System: Angina, arrhythmia, bradycardia, cerebrovascular accident/cerebral infarction, hypertension/hypotension, migraine, myocardial infarction, palpitations, shock (circulatory failure), syncope, tachycardia, vasodilation.

Digestive System: Abnormal stools, anorexia, bezoar, cardiospasm, cholelithiasis, colitis, dry mouth, dyspepsia, dysphagia, enteritis, eructation, esophageal stenosis, esophageal ulcer, esophagitis, faecal discolouration, flatulence, gastric nodules/fundic gland polyps, gastritis, gastroenteritis, gastrointestinal anomaly, gastrointestinal disorder, gastrointestinal haemorrhage, glossitis, gum haemorrhage, haematemesis, increased appetite, increased salivation, melaena, mouth ulceration, nausea and vomiting, nausea and vomiting and diarrhoea, gastrointestinal moniliasis, rectal disorder, rectal haemorrhage, stomatitis, tenesmus, thirst, tongue disorder, ulcerative colitis, ulcerative stomatitis.

Endocrine System: Diabetes mellitus, goitre, hypothyroidism.

Haemic and Lymphatic System: Anaemia, haemolysis, lymphadenopathy.

Metabolic and Nutritional Disorders: Avitaminosis, gout, dehydration, hyperglycaemia/hypoglycaemia, peripheral edema, weight gain/loss.

Musculoskeletal System: Arthralgia, arthritis, bone disorder, joint disorder, leg cramps, musculoskeletal pain, myalgia, myasthenia, ptosis, synovitis.

Nervous System: Abnormal dreams, agitation, amnesia, anxiety, apathy, confusion, convulsion, dementia, depersonalization, depression, diplopia, dizziness, emotional lability, hallucinations, haemiplegia, hostility aggravated, hyperkinesia, hypertonia, hypaesthesia, insomnia, libido decreased/increased, nervousness, neurosis, paraesthesia, sleep disorder, somnolence, thinking abnormality, tremor, vertigo.

Respiratory System: Asthma, bronchitis, cough increased, dyspnoea, epistaxis, haemoptysis, hiccup, laryngeal neoplasia, lung fibrosis, pharyngitis, pleural disorder, pneumonia, respiratory disorder, upper respiratory inflammation/infection, rhinitis, sinusitis, stridor.

Skin and Appendages: Acne, alopecia, contact dermatitis, dry skin, fixed eruption, hair disorder, maculopapular rash, nail disorder, pruritus, rash, skin carcinoma, skin disorder, sweating, urticaria.

Special Senses: Abnormal vision, amblyopia, blepharitis, blurred vision, cataract, conjunctivitis, deafness, dry eyes, ear/eye disorder, eye pain, glaucoma, otitis media, parosmia, photophobia, retinal degeneration/disorder, taste loss, taste perversion, tinnitus, visual field defect.

Urogenital System: Abnormal menses, breast enlargement, breast pain, breast tenderness, dysmenorrhoea, dysuria, gynaecomastia, impotence, kidney calculus, kidney pain, leucorrhoea, menorrhagia, menstrual disorder, penis disorder, polyuria, testis disorder, urethral pain, urinary frequency, urinary retention, urinary tract infection, urinary urgency, urination impaired, vaginitis.

Postmarketing Experience

Additional adverse experiences have been reported since lansoprazole has been marketed. The majority of these cases are foreign-sourced and a relationship to lansoprazole has not been established. Because these reactions were reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events are listed below by the COSTART body system:

Body as a Whole: Anaphylactic/anaphylactoid reactions, systemic lupus erythematosus.

Digestive System: Hepatotoxicity, pancreatitis, vomiting.

Hemic and Lymphatic System: Agranulocytosis, aplastic anaemia, haemolytic anaemia, leucopenia, neutropenia, pancytopenia, thrombocytopenia and thrombotic thrombocytopenic purpura.

Infections and Infestations: Clostridium difficile associated diarrhea.

Metabolism and Nutritional Disorders: Hypomagnesaemia.

Musculoskeletal System: Bone fracture, myositis.

Skin and Appendages: Severe dermatologic reactions, including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal), cutaneous lupus erythematosus

Special Senses: Speech disorder.

Urogenital System: Interstitial nephritis, urinary retention.

Combination Therapy with Amoxicillin and Clarithromycin

In clinical trials using combination therapy with lansoprazole plus amoxicillin and clarithromycin, and lansoprazole plus amoxicillin, no adverse reactions peculiar to these drug combinations were observed. Adverse reactions that have occurred have been limited to those that had been previously reported with lansoprazole, amoxicillin or clarithromycin.

Triple Therapy: Lansoprazole/Amoxicillin/Clarithromycin

The most frequently reported adverse reactions for patients who received triple therapy for 14 days were diarrhoea (7%), headache (6%), and taste perversion (5%). There were no statistically significant differences in the frequency of reported adverse reactions between the 10- and 14-day triple therapy regimens. No treatment-emergent adverse reactions were observed at significantly higher rates with triple therapy than with any dual therapy regimen.

Dual Therapy: Lansoprazole/Amoxicillin

The most frequently reported adverse reactions for patients who received lansoprazole three times daily plus amoxicillin three times daily dual therapy were diarrhoea (8%) and headache (7%). No treatment-emergent adverse reactions were observed at significantly higher rates with lansoprazole three times daily plus amoxicillin three times daily dual therapy than with lansoprazole alone.

For information on adverse reactions with amoxicillin or clarithromycin, refer to their full prescribing information, UNDESIRABLE EFFECTS section.

Laboratory Values

The following changes in laboratory parameters in patients who received lansoprazole were reported as adverse reactions:

Abnormal liver function tests, increased SGOT (AST), increased SGPT (ALT), increased creatinine, increased alkaline phosphatase, increased globulins, increased GGTP, increased/decreased/abnormal WBC, abnormal AG ratio, abnormal RBC, bilirubinaemia, blood potassium increased, blood urea increased, crystal urine present, eosinophilia, haemoglobin decreased, hyperlipaemia, increased/decreased electrolytes, increased/decreased cholesterol, increased glucocorticoids, increased LDH, increased/decreased/abnormal platelets, increased gastrin levels and positive faecal occult blood. Urine abnormalities such as albuminuria, glycosuria and haematuria were also reported. Additional isolated laboratory abnormalities were reported.

In the placebo-controlled studies, when SGOT (AST) and SGPT (ALT) were evaluated, 0.4% (4/978) and 0.4% (11/2,677) patients, who received placebo and lansoprazole, respectively, had enzyme elevations greater than three times the upper limit of normal range at the final treatment visit. None of these patients who received lansoprazole reported jaundice at any time during the study.

In clinical trials using combination therapy with lansoprazole plus amoxicillin and clarithromycin, and lansoprazole plus amoxicillin, no increased laboratory abnormalities particular to these drug combinations were observed.

For information on laboratory value changes with amoxicillin or clarithromycin, refer to their full prescribing information, UNDESIRABLE EFFECTS section.