Lansoprazole: Package Insert and Label Information (Page 3 of 11)

6.2 Postmarketing Experience

Additional adverse experiences have been reported since lansoprazole delayed-release orally disintegrating tablets have been marketed. The majority of these cases are foreign-sourced and a relationship to lansoprazole delayed-release orally disintegrating tablets 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 COSTART body system.

Body as a Whole: anaphylactic/anaphylactoid reactions, systemic lupus erythematosus;

Digestive System: hepatotoxicity, pancreatitis, vomiting;

Hemic and Lymphatic System: agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic purpura;

Infections and Infestations: Clostridium difficile -associated diarrhea;

Metabolism and Nutritional Disorders: hypomagnesemia, hypocalcemia, hypokalemia, hyponatremia;

Musculoskeletal System: bone fracture, myositis;

Skin and Appendages: severe dermatologic reactions including erythema multiforme, SJS/TEN (some fatal), DRESS, AGEP, cutaneous lupus erythematosus;

Special Senses: speech disorder;

Urogenital System: interstitial nephritis, urinary retention.

6.3 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 diarrhea (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 diarrhea (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 about adverse reactions with antibacterial agents (amoxicillin and clarithromycin) indicated in combination with lansoprazole delayed-release orally disintegrating tablets, refer to the Adverse Reactions section of their prescribing information.

6.4 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, bilirubinemia, blood potassium increased, blood urea increased, crystal urine present, eosinophilia, hemoglobin decreased, hyperlipemia, increased/decreased electrolytes, increased/decreased cholesterol, increased glucocorticoids, increased LDH, increased/decreased/abnormal platelets, increased gastrin levels and positive fecal occult blood. Urine abnormalities such as albuminuria, glycosuria, and hematuria 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% (11/2677) 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 about laboratory value changes with antibacterial agents (amoxicillin and clarithromycin) indicated in combination with lansoprazole delayed-release orally disintegrating tablets, refer to the Adverse Reactions section of their prescribing information.

7 DRUG INTERACTIONS

Tables 2 and 3 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with lansoprazole delayed-release orally disintegrating tablets and instructions for preventing or managing them.

Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs.

Table 2. Clinically Relevant Interactions Affecting Drugs Coadministered with Lansoprazole Delayed-Release Orally Disintegrating Tablets and Interactions with Diagnostics

Antiretrovirals

Clinical Impact:

The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known.

Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with lansoprazole may reduce antiviral effect and promote the development of drug resistance.
Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with lansoprazole may increase toxicity of the antiretroviral drugs.
There are other antiretroviral drugs which do not result in clinically relevant interactions with lansoprazole.

Intervention:

Rilpivirine-containing products: Concomitant use with lansoprazole delayed-release orally disintegrating tablets is contraindicated [see Contraindications (4)]. See prescribing information.

Atazanavir: See prescribing information for atazanavir for dosing information.

Nelfinavir: Avoid concomitant use with lansoprazole delayed-release orally disintegrating tablets. See prescribing information for nelfinavir.

Saquinavir: See the prescribing information for saquinavir and monitor for potential saquinavir toxicities.

Other antiretrovirals: See prescribing information.

Warfarin

Clinical Impact:

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.

Intervention:

Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range. See prescribing information for warfarin.

Methotrexate

Clinical Impact:

Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted [see Warnings and Precautions (5.10)].

Intervention:

A temporary withdrawal of lansoprazole delayed-release orally disintegrating tablets may be considered in some patients receiving high-dose methotrexate.

Digoxin

Clinical Impact:

Potential for increased exposure of digoxin.

Intervention:

Monitor digoxin concentrations. Dose adjustment of digoxin may be needed to maintain therapeutic drug concentrations. See prescribing information for digoxin.

Theophylline

Clinical Impact:

Increased clearance of theophylline [see Clinical Pharmacology (12.3)].

Intervention:

Individual patients may require additional titration of their theophylline dosage when lansoprazole delayed-release orally disintegrating tablets are started or stopped to ensure clinically effective blood concentrations.

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole)

Clinical Impact:

Lansoprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity.

Intervention:

Mycophenolate mofetil (MMF): Coadministration 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 lansoprazole and MMF. Use lansoprazole delayed-release orally disintegrating tablets with caution in transplant patients receiving MMF.

See the prescribing information for other drugs dependent on gastric pH for absorption.

Combination Therapy with Clarithromycin and Amoxicillin

Clinical Impact:

Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and are contraindicated. Amoxicillin also has drug interactions.

Intervention:

See Contraindications and Warnings and Precautions in prescribing information for clarithromycin.
See Drug Interactions in prescribing information for amoxicillin.

Tacrolimus

Clinical Impact:

Potentially increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19.

Intervention:

Monitor tacrolimus whole blood trough concentrations. Dose adjustment of tacrolimus may be needed to maintain therapeutic drug concentrations. See prescribing information for tacrolimus.

Interactions with Investigations of Neuroendocrine Tumors

Clinical Impact:

CgA levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors [see Warnings and Precautions (5.9), Clinical Pharmacology (12.2)].

Intervention:

Temporarily stop lansoprazole delayed-release orally disintegrating tablet treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary.

Interaction with Secretin Stimulation Test

Clinical Impact:

Hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma.

Intervention:

Temporarily stop lansoprazole delayed-release orally disintegrating tablet treatment at least 28 days before assessing to allow gastrin levels to return to baseline [see Clinical Pharmacology (12.2)].

False Positive Urine Tests for THC

Clinical Impact:

There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs.

Intervention:

An alternative confirmatory method should be considered to verify positive results.

Table 3. Clinically Relevant Interactions Affecting Lansoprazole Delayed-Release Orally Disintegrating Tablets When Coadministered with Other Drugs

CYP2C19 or CYP3A4 Inducers

Clinical Impact:

Decreased exposure of lansoprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3)].

Intervention:

St John’s Wort, rifampin: Avoid concomitant use with lansoprazole delayed-release orally disintegrating tablets.

Ritonavir-containing products: See prescribing information.

CYP2C19 or CYP3A4 Inhibitors

Clinical Impact:

Increased exposure of lansoprazole is expected when used concomitantly with strong inhibitors [see Clinical Pharmacology (12.3)].

Intervention:

Voriconazole: See prescribing information.

Sucralfate

Clinical Impact:

Decreased and delayed absorption of lansoprazole [see Clinical Pharmacology (12.3)].

Intervention:

Take lansoprazole delayed-release orally disintegrating tablets at least 30 minutes prior to sucralfate [see Dosage and Administration (2.4)].

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