Lansoprazole

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 capsules 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 capsules 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 capsules 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 capsules. 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 capsules 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 capsules is 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 capsules 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 capsules 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 capsules 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 capsules 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 capsules. 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 capsules at least 30 minutes prior to sucralfate [see Dosage and Administration ( 2.4 )]. See full prescribing information for a list of clinically important drug interactions. (7)

Indicated for short-term treatment of active duodenal ulcer, H. pylori eradication (in combination with amoxicillin, with or without clarithromycin), maintenance of healed duodenal ulcers, treatment of active benign gastric ulcer, healing and risk reduction of NSAID-associated gastric ulcer, treatment of symptomatic GERD and erosive esophagitis, maintenance of healed erosive esophagitis, and treatment of pathological hypersecretory conditions including Zollinger-Ellison syndrome.

2 DOSAGE AND ADMINISTRATION Recommended Dosage: See full prescribing information for complete dosing information for lansoprazole delayed-release capsules by indication and age group and dosage adjustment in patients with severe hepatic impairment. ( 2.1 , 2.2 , 2.3 ) Administration Instructions ( 2.4 ) Lansoprazole delayed-release capsules Should be swallowed whole. See full prescribing information for alternative administration options. 2.1 Recommended Adult Dosage by Indication Indication Recommended Dose Frequency Duodenal Ulcers Short-Term Treatment 15 mg Once daily for 4 weeks Maintenance of Healed 15 mg Once daily Eradication of H. pylori to Reduce the Risk of Duodenal Ulcer Recurrence * Triple Therapy: Lansoprazole delayed-release capsules 30 mg Twice daily for 10 or 14 days Amoxicillin 1 gram Twice daily for 10 or 14 days Clarithromycin 500 mg Twice daily for 10 or 14 days Dual Therapy: Lansoprazole delayed-release capsules 30 mg Three times daily for 14 days Amoxicillin 1 gram Three times daily 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 the amoxicillin and clarithromycin full prescribing information, Contraindications and Warnings and Precautions sections, and for information regarding dosing in elderly and renally-impaired patients. † Controlled studies did not extend beyond indicated duration. ‡ For patients who do not heal with lansoprazole delayed-release capsules for eight weeks (5 to 10%), it may be helpful to give an additional eight weeks of treatment. If there is a recurrence of erosive esophagitis, an additional eight week course of lansoprazole delayed-release capsules 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 lansoprazole for more than four years. ¶ Controlled studies did not extend beyond 12 months. 2.2 Recommended Pediatric Dosage by Indication Pediatric Patients 1 to 11 Years of Age In clinical studies, lansoprazole was not administered beyond 12 weeks in 1 to 11 year olds. It is not known if lansoprazole is safe and effective if used longer than the recommended duration. Do not exceed the recommended dose and duration of use in pediatric patients as outlined below [see Use in Specific Populations ( 8.4 )]. Indication Recommended Dose Frequency Short-Term Treatment of Symptomatic GERD and Short-Term Treatment of Erosive Esophagitis ≤ 30 kg 15 mg Once daily for up to 12 weeks >30 kg 30 mg Once daily for up to 12 weeks Pediatric Patients 12 to 17 Years of Age Indication Recommended Dose Frequency Short-Term Treatment of Symptomatic GERD Non-erosive GERD 15 mg Once daily for up to 8 weeks Erosive Esophagitis 30 mg Once daily for up to 8 weeks 2.3 Hepatic Impairment The recommended dosage is 15 mg orally daily in patients with severe liver impairment (Child-Pugh C) [see Use in Specific Populations ( 8.6 )]. 2.4 Important Administration Information Take lansoprazole delayed-release capsules before meals. Do not crush or chew lansoprazole delayed-release capsules. Take lansoprazole delayed-release capsules at least 30 minutes prior to sucralfate [see Drug Interactions ( 7 )]. Antacids may be used concomitantly with lansoprazole delayed-release capsules. Missed doses: If a dose is missed, administer as soon as possible. However, if the next scheduled dose is due, do not take the missed dose, and take the next dose on time. Do not take two doses at one time to make up for a missed dose. Lansoprazole delayed-release capsules • Swallow whole; do not chew. • For patients who have difficulty swallowing capsules, lansoprazole delayed-release capsules can be opened and administered orally or via a nasogastric tube in the soft foods or liquids specified below. • Administration of lansoprazole in foods or liquids other than those discussed below have not been studied clinically and therefore are not recommended. Administration in Soft Foods (applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears): 1. Open capsule. 2. Sprinkle intact granules on one tablespoon of either applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears. 3. Swallow immediately. Administration in Liquids (apple juice, orange juice or tomato juice): 1. Open capsule. 2. Sprinkle intact granules into a small volume of either apple juice, orange juice or tomato juice (60 mL – approximately two ounces). 3. Mix briefly. 4. Swallow immediately. 5. To ensure complete delivery of the dose, rinse the glass with two or more volumes of juice and swallow the contents immediately. Administration with Apple Juice Through a Nasogastric Tube (≥16 French) 1. Open capsule. 2. Sprinkle intact granules into 40 mL of apple juice. 3. Mix briefly. 4. Using a catheter-tipped syringe, draw up the mixture. 5. Inject through the nasogastric tube into the stomach. 6. Flush with additional apple juice to clear the tube.

In placebo-controlled trials, the most frequent possibly/probably treatment-related adverse reactions (≥1%) were diarrhea (3.8% vs. 2.3% placebo), abdominal pain (2.1% vs. 1.2%), nausea (1.3% vs. 1.2%), and constipation (1.0% vs. 0.4%). Diarrhea incidence was higher (7.4%) in patients receiving the 60 mg dose.