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  • CLASSES

    Compounding Kits Miscellaneous
    Proton Pump Inhibitors/PPIs

    DEA CLASS

    Rx, OTC

    DESCRIPTION

    Proton-pump inhibitor (PPI), gastric antisecretory agent.
    Indicated to treat duodenal and gastric ulcers, erosive esophagitis, GERD, heartburn, ZE syndrome, and NSAID-induced ulcers.
    Combined with antibiotics for eradication of H. pylori.

    COMMON BRAND NAMES

    First-Lansoprazole, Heartburn Relief, Prevacid

    HOW SUPPLIED

    First-Lansoprazole Oral Pwd F/Recon: 0.27g, 0.45g, 0.9g
    Heartburn Relief/Lansoprazole/Prevacid Oral Cap DR Pellets: 15mg, 30mg
    Lansoprazole/Prevacid Oral Tab Orally Dis: 15mg, 30mg

    DOSAGE & INDICATIONS

    For the short-term treatment of frequent dyspepsia or pyrosis (heartburn) that occurs 2 or more times per week.
    Oral dosage (capsules, disintegrating tablets†, or oral suspension†)
    Adults

    15 mg PO once daily for up to 14 days. Full relief may take 1 to 4 days. Reassess if heartburn returns after 14-day treatment regimen. For non-prescription use (self care) patient should not take for more than 14 days or more often than every 4 months unless directed by a physician.

    For the treatment of non-erosive gastroesophageal reflux disease (GERD).
    Oral dosage
    Adults

    15 mg PO once daily 30 to 60 minutes before first meal of the day for up to 8 weeks. Per treatment guidelines, initiate empiric therapy based on a presumptive diagnosis of GERD in the setting of typical symptoms of heartburn and regurgitation. For patients with partial response to once daily therapy, consider lansoprazole 15 mg PO twice daily, 30 to 60 minutes before a meal, or, consider a one-time switch to a different PPI. Refer non-responders for further evaluation. Consider maintenance therapy for patients who continue to have symptoms after PPI discontinuation; the lowest effective dose, including on demand or intermittent therapy should be used with regular assessment of the need for continued PPI therapy. Alternatively, step down maintenance therapy to an H2 blocker is acceptable.

    Children and Adolescents 12 years and older

    15 mg PO once daily in the morning at least 30 minutes before a meal, for up to 8 weeks.

    Children 1 to 11 years weighing 30 kg or more

    30 mg PO once daily in the morning at least 30 minutes before a meal, for up to 12 weeks. Initial doses of 1.4 to 1.5 mg/kg/day PO have been reported in medical literature. The dosage was increased (Max: 30 mg PO twice daily) in some children who were symptomatic after 2 weeks in trials ; however, the usual maximum adult dosage for most indications is 30 mg/day.

    Children 1 to 11 years weighing less than 30 kg

    15 mg PO once daily in the morning at least 30 minutes before a meal, for up to 12 weeks. Alternatively, a dose range of 0.7 to 3 mg/kg/day PO is recommended by the American Academy of Pediatrics (AAP). Initial doses of 1.4 to 1.5 mg/kg/day PO have also been suggested in medical literature.

    Infants older than 10 weeks†

    Limited data are available; an initial dose of 1 to 2 mg/kg/day PO given 30 minutes before a meal has been studied. In a phase I trial, 24 infants received lansoprazole 1 or 2 mg/kg/day for 5 days. It was well tolerated and a decrease in the frequency of gastroesophageal reflux symptoms was observed. In a retrospective analysis, the medical charts of 158 infants who received lansoprazole were reviewed. The median lansoprazole dose was 1.74 mg/kg/day PO. This study did not evaluate clinical outcomes or safety. In a double-blind, placebo-controlled trial of 162 infants (aged 1 to 12 months), lansoprazole was not found to be effective as defined by a more than 50% reduction in either the percent of feedings with a crying/fussing/irritability episode or the duration of a crying/fussing/irritability episode within 1 hour of feeding. Infants received lansoprazole suspension 1 to 1.5 mg/kg/day PO. A study of 30 infants (aged 3 to 7 months) compared 15 mg/day given once daily PO to 7.5 mg/dose given twice daily. The twice-daily regimen produced faster symptom response, but both regimens produced significant improvement in symptoms, compared to the control group. PPIs are not recommended as first-line therapy for symptomatic GERD in otherwise healthy infants (1 to 11 months); nonpharmacologic measures such as diet modification and positioning strategies are recommended. Reserve pharmacologic treatment for use in infants with disease diagnosed by endoscopy (e.g., esophageal erosion).

    Infants 10 weeks and younger†

    Limited data are available. A dose of 0.2 to 0.3 mg/kg/day PO given 30 minutes before a meal for 4 weeks was used in a randomized, placebo controlled trial (n = 52); however, no difference in symptoms was noted between lansoprazole and placebo. Doses up to 2 mg/kg/day PO have been reported. Pharmacokinetic data suggest that infants 10 weeks and younger achieve similar drug exposure after smaller doses compared to older infants due to slower clearance. In a phase I trial, 24 infants (older than 4 weeks) received lansoprazole 1 or 2 mg/kg/day PO for 5 days. It was well tolerated and a decrease in the frequency of gastroesophageal reflux symptoms was observed. PPIs are not recommended as first-line therapy for symptomatic GERD in otherwise healthy infants (1 to 11 months); nonpharmacologic measures such as diet modification and positioning strategies are recommended. Reserve pharmacologic treatment for use in infants with disease diagnosed by endoscopy (e.g., esophageal erosion).

    Neonates†

    Limited data are available describing use in neonates; dosing has not been established. A dose of 0.2 to 0.3 mg/kg/day PO given 30 minutes before a meal for 4 weeks was used in patients 10 weeks and younger in a randomized, placebo controlled trial (n = 52); however, no difference in symptoms was noted between lansoprazole and placebo. Larger doses of 0.5 to 1.5 mg/kg/day PO given in 1 or 2 doses per day have been used in smaller, short-term case series (n = 10 to 24). In one study, 10 premature neonates (mean weight = 1.27 kg, mean postnatal age = 2 weeks) received lansoprazole 1.5 mg/kg/day PO divided into 2 doses. After 7 days of treatment, gastric pH increased but not above 2 in any patient. Based on pharmacokinetic data from 24 neonates and infants, it appears that infants 10 weeks and younger achieve similar drug exposure after smaller doses compared to older infants due to slower clearance.

    For the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.
    Oral dosage (capsules, disintegrating tablets, or oral suspension)
    Adults

    Initially, 60 mg PO once daily in the morning at least 30 minutes before a meal. Individualize dosage and continue treatment for as long as clinically indicated. Some patients with Z-E syndrome have been treated continuously for more than four years. Doses up to 90 mg PO twice daily have been used. If the total dosage is greater than 120 mg/day, give in divided doses.

    For Helicobacter pylori (H. pylori) eradication in the treatment of patients with duodenal ulcer disease (active or a history of duodenal ulcer), stomach ulcers†, dyspepsia†, or gastric mucosa associated lymphoid tissue (MALT) lymphoma†.
    NOTE: The American College of Gastroenterology (ACG) recommends 10 to 14 days of a triple-drug regimen containing a proton pump inhibitor (PPI), clarithromycin, and either amoxicillin or metronidazole. Although 10 to 14 days is recommended, ACG also indicates that giving therapy for 2 weeks may be preferred; a meta-analysis of more than 900 patients found that, as compared to a 7-day regimen, the rate of H. pylori eradication was significantly higher in patients taking triple therapy for 14 days (odds ratio 0.62, 95% CI 0.45 to 0.84). Although not significant, there was a trend towards improved eradication rates with 10 days of therapy vs. 7 days of therapy. The same combination for 14 days continues to be recommended as first line therapy in the 2006 global updates from the Maastricht III Consensus Report.
    NOTE: In populations where H. pylori infection is common (10% or more), patients presenting with non-ulcer dyspepsia should be tested for H. pylori; those found to be H. pylori positive should be started on combination eradication therapy (also see Prevpac monograph).
    NOTE: A large body of data exist to support the importance of H. pylori eradication as the first line treatment of gastric MALT lymphoma. Following H. pylori eradication, long term tumor regression is observed in 60% to 90% of patients.
    In combination with clarithromycin and amoxicillin in adults.
    Oral dosage
    Adults

    30 mg PO twice daily with amoxicillin (1 gram twice daily) and clarithromycin (500 mg twice daily) for 10 to 14 days.

    In combination with clarithromycin and metronidazole in adults†.
    Oral dosage
    Adults

    30 mg PO twice daily with clarithromycin (500 mg twice daily) and metronidazole (500 mg twice daily) for 10 to 14 days is recommended.

    In combination with bismuth, metronidazole, and tetracycline in adults†.
    Oral dosage
    Adults

    30 mg PO twice daily with bismuth subsalicylate (525 mg four times daily), metronidazole (250 mg four times daily), and tetracycline (500 mg four times daily) for 10 to 14 days.

    In combination with amoxicillin in adult patients who are intolerant or resistant to clarithromycin.
    Oral dosage
    Adults

    More effective triple regimens are available. The FDA-approved dual regimen includes: lansoprazole 30 mg PO three times daily plus amoxicillin (1 gram three times daily), given for 14 days. H. pylori eradication rates are lower with this dual regimen (66 to 77%, per-protocol analysis) relative to the 2-week triple regimen containing clarithromycin (85 to 92%, per-protocol analysis).

    In combination with amoxicillin and metronidazole in pediatric patients†.
    Oral dosage
    Children and Adolescents

    1 to 2 mg/kg/day PO divided twice daily (Max: 30 mg/dose) in combination with amoxicillin (25 mg/kg/dose PO twice daily [Max: 1 g/dose]) and metronidazole (10 mg/kg/dose PO twice daily [Max: 500 mg/dose]) for 1 to 2 weeks.

    In combination with amoxicillin and clarithromycin in pediatric patients†.
    Oral dosage
    Children and Adolescents

    1 to 2 mg/kg/day PO divided twice daily (Max: 30 mg/dose) in combination with amoxicillin (25 mg/kg/dose PO twice daily [Max: 1 g/dose]) and clarithromycin (10 mg/kg/dose PO twice daily [Max: 500 mg/dose]) for 1 to 2 weeks.

    As part of a sequential therapy regimen in pediatric patients†.
    Oral dosage
    Children and Adolescents

    1 to 2 mg/kg/day PO divided twice daily (Max: 30 mg/dose) for 10 days; use in combination with amoxicillin (25 mg/kg/dose PO twice daily [Max: 1 g/dose]) for days 1 through 5, and then clarithromycin (10 mg/kg/dose PO twice daily [Max: 500 mg/dose]) and metronidazole (10 mg/kg/dose PO twice daily [Max: 500 mg/dose]) for days 6 through 10.

    For the treatment of active duodenal ulcer.
    NOTE: For dosing in patients with ulcers due to H. pylori, see “H. pylori eradication” indication.
    Oral dosage
    Adults

    15 mg PO once daily in the morning at least 30 minutes before a meal, for up to 4 weeks. For maintenance of remission, 15 mg PO once daily in the morning at least 30 minutes before a meal may be continued; controlled studies did not extend beyond 12 months.

    Children and Adolescents 12 years and older

    15 mg PO once daily in the morning at least 30 minutes before a meal, for up to 4 weeks. For maintenance of remission, 15 mg PO once daily in the morning at least 30 minutes before a meal may be continued; controlled studies did not extend beyond 12 months.

    For the treatment of active benign gastric ulcer.
    NOTE: For dosing in patients with ulcers due to H. pylori, see “H. pylori eradication” indication.
    Oral dosage
    Adults

    30 mg PO once daily in the morning at least 30 minutes before a meal, for up to 8 weeks.

    Children and Adolescents 12 years and older

    30 mg PO once daily in the morning at least 30 minutes before a meal, for up to 8 weeks.

    For the treatment of erosive esophagitis (erosive GERD).
    Oral dosage
    Adults

    30 mg PO once daily 30 to 60 minutes before first meal of the day for up to 8 weeks. If healing is incomplete or recurs, consider an additional 8 weeks of treatment. For maintenance of healing, 15 mg PO once daily 30 to 60 minutes before first meal of the day. Periodically reassess need for continued PPI therapy; controlled studies did not extend beyond 12 months.

    Children and Adolescents 12 years and older

    30 mg PO once daily 30 to 60 minutes before first meal of the day for up to 8 weeks. If healing is incomplete or recurs, consider an additional 8 weeks of treatment. For maintenance of healing, 15 mg PO once daily 30 to 60 minutes before first meal of the day. Periodically reassess need for continued PPI therapy; controlled studies did not extend beyond 12 months.

    Children 1 to 11 years weighing 30 kg or more

    30 mg PO once daily in the morning at least 30 minutes before a meal, for up to 12 weeks. Initial doses of 1.4 to 1.5 mg/kg/day PO have been reported in medical literature. The dosage was increased (Max: 30 mg PO twice daily) in some children who were symptomatic after 2 weeks in trials ; however, the usual maximum adult dosage for most indications is 30 mg/day.

    Children 1 to 11 years weighing less than 30 kg

    15 mg PO once daily in the morning at least 30 minutes before a meal, for up to 12 weeks. Alternatively, a dose range of 0.7 to 3 mg/kg/day PO is recommended by the American Academy of Pediatrics (AAP). Initial doses of 1.4 to 1.5 mg/kg/day PO have also been suggested in medical literature.

    Infants older than 10 weeks†

    Limited data are available; an initial dose of 1 to 2 mg/kg/day PO given 30 minutes before a meal has been studied. In a phase I trial, 24 infants received lansoprazole 1 or 2 mg/kg/day for 5 days. It was well tolerated and a decrease in the frequency of gastroesophageal reflux symptoms was observed. In a retrospective analysis, the medical charts of 158 infants who received lansoprazole were reviewed. The median lansoprazole dose was 1.74 mg/kg/day PO. This study did not evaluate clinical outcomes or safety. In a double-blind, placebo-controlled trial of 162 infants (aged 1 to 12 months), lansoprazole was not found to be effective as defined by a more than 50% reduction in either the percent of feedings with a crying/fussing/irritability episode or the duration of a crying/fussing/irritability episode within 1 hour of feeding. Infants received lansoprazole suspension 1 to 1.5 mg/kg/day PO. A study of 30 infants (aged 3 to 7 months) compared 15 mg/day given once daily PO to 7.5 mg/dose given twice daily. The twice-daily regimen produced faster symptom response, but both regimens produced significant improvement in symptoms, compared to the control group. PPIs are not recommended as first-line therapy for symptomatic GERD in otherwise healthy infants (1 to 11 months); nonpharmacologic measures such as diet modification and positioning strategies are recommended. Reserve pharmacologic treatment for use in infants with disease diagnosed by endoscopy (e.g., esophageal erosion).

    Infants 10 weeks and younger†

    Limited data are available. A dose of 0.2 to 0.3 mg/kg/day PO given 30 minutes before a meal for 4 weeks was used in a randomized, placebo controlled trial (n = 52); however, no difference in symptoms was noted between lansoprazole and placebo. Doses up to 2 mg/kg/day PO have been reported. Pharmacokinetic data suggest that infants 10 weeks and younger achieve similar drug exposure after smaller doses compared to older infants due to slower clearance. In a phase I trial, 24 infants (older than 4 weeks) received lansoprazole 1 or 2 mg/kg/day PO for 5 days. It was well tolerated and a decrease in the frequency of gastroesophageal reflux symptoms was observed. PPIs are not recommended as first-line therapy for symptomatic GERD in otherwise healthy infants (1 to 11 months); nonpharmacologic measures such as diet modification and positioning strategies are recommended. Reserve pharmacologic treatment for use in infants with disease diagnosed by endoscopy (e.g., esophageal erosion).

    Neonates†

    Limited data are available describing use in neonates; dosing has not been established. A dose of 0.2 to 0.3 mg/kg/day PO given 30 minutes before a meal for 4 weeks was used in patients 10 weeks and younger in a randomized, placebo controlled trial (n = 52); however, no difference in symptoms was noted between lansoprazole and placebo. Larger doses of 0.5 to 1.5 mg/kg/day PO given in 1 or 2 doses per day have been used in smaller, short-term case series (n = 10 to 24). In one study, 10 premature neonates (mean weight = 1.27 kg, mean postnatal age = 2 weeks) received lansoprazole 1.5 mg/kg/day PO divided into 2 doses. After 7 days of treatment, gastric pH increased but not above 2 in any patient. Based on pharmacokinetic data from 24 neonates and infants, it appears that infants 10 weeks and younger achieve similar drug exposure after smaller doses compared to older infants due to slower clearance.

    Intravenous infusion dosage
    Adults

    30 mg IV once daily infused over 30 minutes for up to 7 days. Switch to oral therapy when feasible. Oral and IV lansoprazole equally suppress acid production.

    For NSAID-induced ulcer prophylaxis or healing.
    To treat an active NSAID-associated gastric ulcer in patients who continue NSAID use.
    Oral dosage
    Adults

    30 mg PO once daily in the morning at least 30 minutes before a meal for 8 weeks.

    To reduce the risk of NSAID-associated ulcers in patients with a prior documented gastric ulcer and who require NSAID therapy.
    Oral dosage
    Adults

    15 mg PO once daily in the morning at least 30 minutes before a meal. A higher dosage of 30 mg once daily has been evaluated for risk-reduction of NSAID-induced ulcers in a large multicenter trial; the larger dose yielded no additional benefit compared to the 15 mg dose.

    For stress gastritis prophylaxis† in critically-ill patients.
    Nasogastric dosage (lansoprazole oral capsule)
    Adults

    30 mg lansoprazole once daily via nasogastric tube. May open capsule and pour one-quarter of the granules into a nasogastric feeding syringe with the plunger removed. Slowly add water through the plunger end and push the water and granules through the tube by depressing the plunger. Repeat the process until all the granules are administered; flush tube with 15 mL of water to administer any residual granules. The effect of daily nasogastric lansoprazole on acid suppression was evaluated via continuos intragastric pH-metry for 3 days in 15 critically ill patients. After 2 days of lansoprazole therapy, the mean percentage of intragastric pH measurements of 4 or greater increased from 25% (+/- 13%) at baseline to 84% (+/- 14%) (p = 0.001).

    Nasogastric dosage (lansoprazole oral disintegrating tablet)
    Adults

    30 mg lansoprazole orally disintegrating tablet (ODT) once daily via nasogastric tube. Mix a 30 mg ODT in 10 mL of water, administer via nasogastric tube; flush tube with 10 mL of sterile water and clamp for 60 minutes. The effect of daily enteral lansoprazole was compared to that of IV lansoprazole in a study including 19 critically ill patients requiring stress ulcer prophylaxis. Enteral LODT maintained gastric pH measurements of 4 or greated for a duration longer than IV lansoprazole at both 24 hours (7.4 vs. 5.9 hr; p = 0.039) and 72 hours (10.4 vs. 8.9 hr; p = 0.046).

    For the treatment of proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE) in the differential diagnosis of eosinophilic esophagitis (EoE)†.
    Oral dosage
    Adults

    Proton Pump Inhibitor (PPI) dosing in the range of 20 mg to 40 mg PO twice daily 30 to 60 minutes before meals has been studied; treat for up to 8 weeks and continue until the time of the follow-up endoscopy and biopsy. For lansoprazole, it is practical to give 30 mg/dose, due to marketed dosage forms available. According to guidelines, a PPI trial is central to the differential diagnosis of EoE. If eosinophilia and symptoms persist on repeat endoscopy and biopsy following a PPI trial, then EoE can be formally diagnosed. If symptoms and eosinophilia resolve, then PPI-REE is diagnosed; PPI-REE patients may or may not have underlying GERD. More than one-third of all patients with esophageal eosinophilia on biopsy will respond to a PPI.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    30 mg/day PO for most indications; 90 mg/day PO for eradication of H. pylori; up to 180 mg/day PO for Zollinger-Ellison syndrome.

    Geriatric

    30 mg/day PO for most indications; 90 mg/day PO for eradication of H. pylori; up to 180 mg/day PO for Zollinger-Ellison syndrome.

    Adolescents

    30 mg/day PO for most indications; up to 60 mg/day PO has been used off-label for eradication of H. pylori.

    Children

    12 years: 30 mg/day PO for most indications; up to 60 mg/day PO has been used off-label for eradication of H. pylori.
    1 to 11 years weighing more than 30 kg: 30 mg/day PO for GERD or erosive esophagitis, up to 60 mg/day PO has been used off-label for refractory cases and for eradication of H. pylori.
    1 to 11 years weighing 30 kg or less: 15 mg/day PO for GERD or erosive esophagitis, occasionally higher doses used for refractory cases; up to 2 mg/kg/day (Max: 60 mg/day) PO has been used off-label for eradication of H. pylori.

    Infants

    Safety and efficacy have not been established; doses up to 2 mg/kg/day PO have been used off-label for GERD.

    Neonates

    Safety and efficacy have not been established; doses up to 1.5 mg/kg/day have been used off-label for GERD.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Consider dosage reduction in patients with severe hepatic disease; specific recommendations are not available. In patients with chronic hepatic impairment, an increase in the mean AUC of up to 500% was observed at steady state compared to healthy subjects.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
     
    Intermittent hemodialysis
    Lansoprazole is not removed by hemodialysis.

    ADMINISTRATION

    For storage information, see specific product information within the How Supplied section.

    Oral Administration

    All oral dosage forms: Administer on an empty stomach, 30—60 minutes before meals. If given once daily, administer before the first meal of the day. Antacids were used concomitantly with lansoprazole in clinical trials.

    Oral Solid Formulations

    Delayed-release capsules: Swallow delayed-release capsules intact; do not chew or crush. For patients with difficulty swallowing, the capsules may be opened and the contents sprinkled on 1 tablespoonful (15 ml) of either applesauce, Ensure pudding, yogurt, cottage cheese, or strained pears. Do not crush the capsule contents into the food. Swallow immediately. Do not chew the medication. Do not prepare doses before the time of administration. Alternatively, the capsule may be emptied into a small volume of either apple juice, orange juice, or tomato juice (60 ml, approximately 2 ounces), mixed briefly and swallowed immediately. To ensure complete delivery of the dose, the glass should be rinsed with two or more volumes of juice and the contents swallowed immediately. The granules have been shown in vitro to remain intact when exposed to apple, cranberry, grape, orange, pineapple, prune, tomato, and V-8 vegetable juice and stored for up to 30 minutes.
    Delayed-release disintegrating tablets: Place on the tongue and allow to disintegrate until the particles can be swallowed. The tablet will disintegrate rapidly (< 1 minute). Do not cut, chew, or crush the tablets. For administration via an oral syringe, the tablet can be dissolved in water (4 ml for 15 mg tablet, 10 ml for 30 mg tablet) and should be administered within 15 minutes.
    Patients with a nasogastric tube: Prevacid capsules or disintegrating tablets can be administered via a nasogastric tube. Capsules: Open the capsule and mix the intact granules in 40 ml of apple juice and inject through the nasogastric tube into the stomach. After administration, flush the nasogastric tube with additional apple juice to clear the tube. Disintegrating tablets: Dissolve tablet in water (4 ml for 15 mg tablet, 10 ml for 30 mg tablet) and administer within 15 minutes. After administration, flush the tube to clear it.

    Oral Liquid Formulations

    Delayed-release oral suspension: Packets containing the enteric-coated granules (15 or 30 mg doses) are mixed with 2 tablespoonfuls (30 ml) of water to form a strawberry-flavored suspension intended for immediate administration after mixing. Do not use with other liquids or foods. Stir well and drink immediately. Do not crush or chew the granules. If any material remains after drinking, add more water, stir, and drink immediately.

    Extemporaneous Compounding-Oral

    Extemporaneous preparation of oral suspension ('simplified lansoprazole suspension' or SLS):
    NOTE: The extemporaneous preparation of lansoprazole suspension is not approved by the FDA.
    Empty the contents of one 30 mg lansoprazole capsule into an empty 15 ml syringe with needle in place (plunger removed). Then, replace the plunger and uncap the needle. Withdraw 10 ml of sodium bicarbonate 8.4% (1 mEq/ml) solution from a sodium bicarbonate vial. Gently shake syringe for 10 to 15 minutes, until the granules dissolve and a white suspension of lansoprazole is obtained.
    Extended stability data are not available; it is recommended that SLS be used immediately following preparation.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Administer as an intravenous (IV) infusion. Do NOT administer by IV push or other parenteral routes.
     
    Reconstitution of vial
    Reconstitute each 30 mg vial with 5 ml of Sterile Water for Injection, USP only. NOTE: Lansoprazole IV must be reconstituted with 5 ml of Sterile Water for Injection, USP. Failure to reconstitute with Sterile Water may result in formation of precipitation/particulates.
    Mix gently by swirling. The resulting solution will contain lansoprazole 6 mg/ml.
    The reconstituted solution can be held for 1 hour when stored at 25 degrees C (77 degrees F) prior to further dilution.
    Reconstituted vials and admixtures do not need to be protected from light. Do not freeze.
    Preparation and Administration of IV infusion
    Dilute the reconstituted vial in either 50 ml of 0.9% Sodium Chloride Injection (NS), Lactated Ringer's Injection (LR), or 5% Dextrose Injection (D5W). Store the admixture at 25 degrees C (77 degrees F). No refrigeration is required.
    If reconstituted with NS or LR, solution must be administered within 24 hours. If reconstituted with D5W, solution must be administered within 12 hours.
    Administer using the in-line filter provided. The filter MUST be used to remove precipitate.
    Administered either through a dedicated line or a Y-site. A dedicated line is not required; however, the IV line should be flushed before and after administration. When administered via a Y-site, immediately stop use if a precipitation or discoloration occurs.
    Infuse over 30 minutes.

    STORAGE

    First-Lansoprazole:
    - Protect from freezing
    - Protect from light
    - Store at room temperature (between 59 to 86 degrees F)
    - Store reconstituted product in refrigerator (between 36 to 46 degrees F) for up to 30 days
    Heartburn Relief:
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Prevacid:
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Antimicrobials, lansoprazole, omeprazole, and bismuth preparations suppress H. pylori. Ingestion of these substances within four (4) weeks prior to performing urease or breath-tests for H. pylori detection may lead to false negative results. In the four weeks prior to performing the test, the patient must avoid the use lansoprazole and other agents which are known to suppress H. pylori.

    Proton pump inhibitors (PPIs) hypersensitivity

    Lansoprazole is contraindicated in patients who have shown lansoprazole hypersensitivity. Lansoprazole is a proton pump inhibitor (PPI) and should be used with caution in patients with known proton pump inhibitors (PPIs) hypersensitivity. There has been evidence of PPI cross-sensitivity in some sensitive individuals in literature reports. Although rare, occasionally such reactions can be serious (e.g., result in anaphylaxis, angioedema, or acute interstitial nephritis).

    Vitamin B12 deficiency

    Daily treatment with gastric acid-suppressing medication such as lansoprazole over a long period of time (e.g., generally >= 2—3 years) may lead to malabsorption of cyanocobalamin and vitamin B12 deficiency. Cases of cyanocobalamin deficiency occurring with acid-suppression therapy have been reported in the literature. One large case-controlled study compared patients with and without an incident diagnosis of vitamin B12 deficiency. A correlation was demonstrated between vitamin B12 deficiency and gastric acid-suppression therapy of > 2 years duration [i.e., proton pump inhibitor (PPI), H2-receptor antagonist]. In addition, a dose-dependant relationship was evident, as larger daily PPI pill counts were more strongly associated with vitamin B12 deficiency. The possibility of cyanocobalamin deficiency should, therefore, be considered if clinical symptoms are observed.

    Hepatic disease

    Lansoprazole elimination half-life is significantly prolonged in patients with hepatic disease. In patients with severe hepatic disease, dosage reduction of lansoprazole should be considered. Abnormal liver-function tests have been reported infrequently with lansoprazole use.

    Diarrhea, pseudomembranous colitis

    The use of gastric acid suppressive therapy, such as PPIs, may increase the risk of enteric infection by encouraging the growth of gut microflora and increasing susceptibility to organisms including Salmonella, Campylobacter jejuni, Escherichia coli, Clostridium difficile, Vibrio cholerae, and Listeria. A systematic review examined the relationship between PPI use and susceptibility to enteric infections and found enhanced susceptibility for Salmonella infections (adjusted RR range: 4.2—8.3 in 2 studies), Campylobacter (RR 3.5—11.7 in 4 studies) and C. difficile infections (RR 1.2—5.0 in 17 out of 27 studies). In particular, PPI use has been linked to an increased risk of Clostridium difficile–associated diarrhea (CDAD). A diagnosis of CDAD should be considered for patients taking PPIs who develop diarrhea that does not improve. Advise patients to seek immediate care from a healthcare professional if they experience watery stool that does not go away, abdominal pain, and fever while taking PPIs. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. The PPIs, including lansoprazole, are recommended for use in combination with certain antibiotics to eradicate Helicobacter pylori. Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents in combination with PPIs.

    Gastric cancer

    Symptomatic response to therapy with lansoprazole does not preclude the presence of gastric cancer or other malignancy.

    Bone fractures, geriatric, osteoporosis

    Use proton pump inhibitors (PPIs) in patients with or who have risk factors for osteoporosis cautiously. PPIs have been associated with a possible increased risk of bone fractures of the hip, wrist, and spine. Epidemiological studies have reported an increased risk of fractures with the use of PPIs; the studies compared claims data of patients treated with PPIs versus individuals who were not using PPIs. The risk of fracture was increased in patients who received high-dose (defined as multiple daily doses or doses greater than those recommended in non-prescription use), and long-term PPI therapy (a year or longer); fractures were primarily observed in older adult and geriatric patients 50 years of age and older. It should be noted that pre-approval randomized clinical trials (RCTs) of PPIs have not found an increased risk of fractures of the hip, wrist, or spine; however, these RCTs were of shorter study duration (generally 6 months or less). When prescribing PPIs, consider whether a lower dose or shorter duration of therapy would adequately treat the patient's condition. In patients with or at risk for osteopenia or osteoporosis, manage their bone status according to current clinical practice, and ensure adequate vitamin D and calcium supplementation. According to the Beers Criteria, PPIs are considered potentially inappropriate medications (PIMs) for use in geriatric patients due to the risk of Clostridium difficile and bone loss/fractures. Scheduled use for more than 8 weeks should be avoided except for high-risk patients (e.g., oral corticosteroids or chronic NSAID use), erosive esophagitis, Barrett's esophagitis, pathological hypersecretory condition, or demonstrated need for maintenance treatment (e.g., due to failure of drug discontinuation trial or H-2 blockers).

    Hypomagnesemia, long QT syndrome

    Daily treatment with a gastric acid-suppressing medication over a long period of time (e.g., 3 months to > 1 year) may lead to hypomagnesemia; cases have been reported in patients taking lansoprazole. Generally, hypomagnesemia is corrected with magnesium supplementation; however, in cases where hypomagnesemia is observed during PPI administration, discontinuation of the PPI may also be necessary. Low serum magnesium may lead to serious adverse events such as muscle spasm (tetany), seizures, and irregular heartbeat (arrhythmias). Use PPIs with caution and, if possible, avoid long-term (> 14 days) use in patients with congenital long QT syndrome, as they may be at higher risk for arrhythmias. In pediatric patients, irregular heartbeat may cause fatigue, upset stomach, dizziness, and lightheadedness. For patients expected to be on PPI therapy for a prolonged period of time, it is prudent for clinicians to obtain serum magnesium concentrations prior to initiating PPI therapy as well as throughout treatment. Patients on concomitant medications such as digoxin or diuretics (see Interactions) may also require periodic monitoring of serum magnesium.

    Rebound acid hypersecretion

    Studies suggest that long-term PPI therapy is associated with a temporal increase in gastric acid secretion shortly following treatment discontinuation. A similar and well established response has been noted after withdrawal of H2 blockers. Profound gastric acid suppression during PPI therapy leads to a drug-induced reflex hypergastrinemia and subsequent rebound acid hypersecretion. In this hypersecretory state, enterochromaffin-like cell hypertrophy also results in a temporal increase in serum chromogranin A (CgA) levels. It is unclear, however, if this hypersecretory reflex results in clinically significant effects in patients on or attempting to discontinue PPI therapy. A clinically significant effect may lead to gastric acid-related symptoms upon PPI withdrawal and possible therapy dependence. Studies in healthy subjects (H. pylori negative) as well as GERD patients, present conflicting data regarding whether PPI therapy beyond 8-weeks is associated with rebound acid hypersecretion and associated dyspeptic symptoms shortly following PPI cessation. Until more consistent study results shed light on this possible effect, it is prudent to follow current treatment guidelines employing the lowest effective dose, for the shortest duration of time in symptomatic patients. For patients requiring maintenance therapy, consider on demand or intermittent PPI therapy, step down therapy to an H2 blocker, and regularly assess the need for continued gastric suppressive therapy.

    Pregnancy

    Lansoprazole is classified in FDA pregnancy risk category B. There are no adequate or well-controlled studies in pregnant women. Animal reproductive studies at doses up to 40 times the recommended human dose based on body surface area, revealed no evidence of impaired fertility or fetal harm. It is not known if lansoprazole crosses the human placenta; its low molecular weight (359) suggests that it has the potential to do so. Cases of inadvertent exposure and therapeutic use of lansoprazole in early gestation in humans suggest a low risk to the fetus. Nevertheless, human pregnancy data are limited and avoidance of lansoprazole as with all PPIs, especially during the first trimester, is the safest course. Lansoprazole should be used during pregnancy only when the severity of the patient's condition clearly indicates a necessity for its use. In 2009, a population-based observational cohort study explored a possible link between gastric acid suppressive therapy (e.g., proton pump inhibitors) during pregnancy and a diagnosis of allergic disease or a prescription for asthma or allergy medications in the exposed child. Among the cohort (n = 585,716), 1% of children exposed to gastric acid suppressive drugs in pregnancy received a diagnosis of allergic diease. For developing allergy or asthma, an increased OR of 1.43 and 1.51, respectively, were observed regardless of drug used, time of exposure during pregnancy, and maternal history of disease. Proposed possible mechanisms for a link include: (1) exposure to increased amounts of allergens could cause sensitization to digestion-labile antigens in the fetus; (2) the maternal Th2 cytokine pattern could promote an allergy prone phenotype in the fetus; (3) maternal allergen specific immunoglobulin could cross the placenta and sensitize fetal immune cells to food and airborne allergens. Study limitations were present and confirmation of results are necessary before further conclusions can be drawn from this data. Risk versus benefit should be considered prior to use.

    Breast-feeding

    Animal studies indicate that lansoprazole is excreted into breast milk. No studies have been done to determine if lansoprazole is similarly excreted into human milk. Because of the potential for suppression of gastric acid secretion or other effects in the nursing infant, lansoprazole use should be avoided during breast-feeding. A decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother's condition. Alternative therapies for consideration include antacids and H2 blockers.

    Phenylketonuria

    Patients with phenylketonuria should be made aware that lansoprazole disintegrating tablets contain phenylalanine (2.5 mg per 15 mg tablet; 5.1 mg per 30 mg tablet). The capsule and syrup formulations do not contain phenylalanine.

    Infants, neonates

    The safety and efficacy of lansoprazole has not been established in neonates or infants; however, the drug has been used off-label with caution in these populations. According to the manufacturer, a multicenter, double-blind, placebo controlled study including infants (1 month to < 1 year of age) with symptomatic GERD failed to show safety and efficacy. Limited data are available describing lansoprazole use in neonates.

    Systemic lupus erythematosus (SLE)

    Use with caution in patients with a history of systemic lupus erythematosus (SLE) as lansoprazole has been reported to activate or exacerbate SLE.

    ADVERSE REACTIONS

    Severe

    esophageal ulceration / Delayed / 0-1.0
    GI bleeding / Delayed / 0-1.0
    bezoar / Delayed / 0-1.0
    hematemesis / Delayed / 0-1.0
    seizures / Delayed / 0-1.0
    bronchospasm / Rapid / 0-1.0
    hearing loss / Delayed / 0-1.0
    stroke / Early / 0-1.0
    myocardial infarction / Delayed / 0-1.0
    bradycardia / Rapid / 0-1.0
    arrhythmia exacerbation / Early / 0-1.0
    pancreatitis / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    interstitial nephritis / Delayed / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    bone fractures / Delayed / Incidence not known
    hyperkalemia / Delayed / Incidence not known

    Moderate

    constipation / Delayed / 1.0-5.0
    dysphagia / Delayed / 0-1.0
    melena / Delayed / 0-1.0
    esophagitis / Delayed / 0-1.0
    glossitis / Early / 0-1.0
    stomatitis / Delayed / 0-1.0
    gastritis / Delayed / 0-1.0
    amblyopia / Delayed / 0-1.0
    depression / Delayed / 0-1.0
    hallucinations / Early / 0-1.0
    migraine / Early / 0-1.0
    amnesia / Delayed / 0-1.0
    confusion / Early / 0-1.0
    hypertonia / Delayed / 0-1.0
    hostility / Early / 0-1.0
    cholelithiasis / Delayed / 0-1.0
    lymphadenopathy / Delayed / 0-1.0
    hemolysis / Early / 0-1.0
    anemia / Delayed / 0-1.0
    contact dermatitis / Delayed / 0-1.0
    colitis / Delayed / 0-1.0
    hemoptysis / Delayed / 0-1.0
    dyspnea / Early / 0-1.0
    vaginitis / Delayed / 0-1.0
    urinary retention / Early / 0-1.0
    impotence (erectile dysfunction) / Delayed / 0-1.0
    dysuria / Early / 0-1.0
    urethral pain / Early / 0-1.0
    synovitis / Delayed / 0-1.0
    myasthenia / Delayed / 0-1.0
    dehydration / Delayed / 0-1.0
    hypoglycemia / Early / 0-1.0
    goiter / Delayed / 0-1.0
    blepharitis / Early / 0-1.0
    diabetes mellitus / Delayed / 0-1.0
    blurred vision / Early / 0-1.0
    hypothyroidism / Delayed / 0-1.0
    hyperglycemia / Delayed / 0-1.0
    cataracts / Delayed / 0-1.0
    candidiasis / Delayed / 0-1.0
    gout / Delayed / 0-1.0
    conjunctivitis / Delayed / 0-1.0
    photophobia / Early / 0-1.0
    chest pain (unspecified) / Early / 0-1.0
    angina / Early / 0-1.0
    sinus tachycardia / Rapid / 0-1.0
    peripheral edema / Delayed / 0-1.0
    hypertension / Early / 0-1.0
    edema / Delayed / 0-1.0
    hypotension / Rapid / 0-1.0
    palpitations / Early / 0-1.0
    elevated hepatic enzymes / Delayed / 0.4-0.4
    hyperbilirubinemia / Delayed / Incidence not known
    vitamin B12 deficiency / Delayed / Incidence not known
    hyperuricemia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    pernicious anemia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    glycosuria / Early / Incidence not known
    hematuria / Delayed / Incidence not known
    hypomagnesemia / Delayed / Incidence not known
    hyperlipidemia / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known

    Mild

    diarrhea / Early / 1.0-7.4
    headache / Early / 1.0-7.0
    abdominal pain / Early / 0-2.1
    nausea / Early / 1.3-1.3
    appetite stimulation / Delayed / 0-1.0
    anorexia / Delayed / 0-1.0
    vomiting / Early / 0-1.0
    tenesmus / Delayed / 0-1.0
    stool discoloration / Delayed / 0-1.0
    halitosis / Early / 0-1.0
    dyspepsia / Early / 0-1.0
    xerostomia / Early / 0-1.0
    eructation / Early / 0-1.0
    flatulence / Early / 0-1.0
    hypersalivation / Early / 0-1.0
    dysgeusia / Early / 0-1.0
    vertigo / Early / 0-1.0
    diplopia / Early / 0-1.0
    drowsiness / Early / 0-1.0
    anxiety / Delayed / 0-1.0
    dizziness / Early / 0-1.0
    tremor / Early / 0-1.0
    paresthesias / Delayed / 0-1.0
    libido increase / Delayed / 0-1.0
    hypoesthesia / Delayed / 0-1.0
    insomnia / Early / 0-1.0
    hyperkinesis / Delayed / 0-1.0
    parosmia / Delayed / 0-1.0
    libido decrease / Delayed / 0-1.0
    agitation / Early / 0-1.0
    emotional lability / Early / 0-1.0
    pruritus / Rapid / 0-1.0
    rash (unspecified) / Early / 0-1.0
    urticaria / Rapid / 0-1.0
    maculopapular rash / Early / 0-1.0
    xerosis / Delayed / 0-1.0
    alopecia / Delayed / 0-1.0
    diaphoresis / Early / 0-1.0
    acne vulgaris / Delayed / 0-1.0
    injection site reaction / Rapid / 1.0-1.0
    rhinitis / Early / 0-1.0
    cough / Delayed / 0-1.0
    epistaxis / Delayed / 0-1.0
    sinusitis / Delayed / 0-1.0
    pharyngitis / Delayed / 0-1.0
    hiccups / Early / 0-1.0
    menorrhagia / Delayed / 0-1.0
    polyuria / Early / 0-1.0
    dysmenorrhea / Delayed / 0-1.0
    increased urinary frequency / Early / 0-1.0
    menstrual irregularity / Delayed / 0-1.0
    leukorrhea / Delayed / 0-1.0
    pelvic pain / Delayed / 0-1.0
    arthralgia / Delayed / 0-1.0
    myalgia / Early / 0-1.0
    back pain / Delayed / 0-1.0
    muscle cramps / Delayed / 0-1.0
    musculoskeletal pain / Early / 0-1.0
    gynecomastia / Delayed / 0-1.0
    malaise / Early / 0-1.0
    weight loss / Delayed / 0-1.0
    xerophthalmia / Early / 0-1.0
    chills / Rapid / 0-1.0
    ocular pain / Early / 0-1.0
    asthenia / Delayed / 0-1.0
    fever / Early / 0-1.0
    ptosis / Delayed / 0-1.0
    weight gain / Delayed / 0-1.0
    breast enlargement / Delayed / 0-1.0
    mastalgia / Delayed / 0-1.0
    tinnitus / Delayed / 0-1.0
    syncope / Early / 0-1.0
    infection / Delayed / Incidence not known
    fatigue / Early / Incidence not known
    hoarseness / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Butalbital: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Acetaminophen; Butalbital; Caffeine: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Acetaminophen; Butalbital; Caffeine; Codeine: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Afatinib: If the concomitant use of lansoprazole and afatinib is necessary, consider reducing the afatinib dose by 10 mg per day if the original dose is not tolerated; resume the previous dose of afatinib as tolerated after discontinuation of lansoprazole. Afatinib is a P-glycoprotein (P-gp) substrate and inhibitor in vitro, and lansoprazole is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration of another P-gp inhibitor, ritonavir (200 mg twice daily for 3 days), 1 hour before afatinib (single dose) increased the afatinib AUC and Cmax by 48% and 39%, respectively; there was no change in the afatinib AUC when ritonavir was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with ritonavir, and 111% and 105% when ritonavir was administered 6 hours after afatinib. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise.
    Alendronate: Proton pump inhibitors (PPIs) are widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use proton pump inhibitors in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. It is not yet clear if all bisphosphonates would exhibit a loss of efficacy when PPIs are coadministered, but the results suggest that the interaction may occur across the class.
    Alendronate; Cholecalciferol: Proton pump inhibitors (PPIs) are widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use proton pump inhibitors in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. It is not yet clear if all bisphosphonates would exhibit a loss of efficacy when PPIs are coadministered, but the results suggest that the interaction may occur across the class.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Aliskiren; Hydrochlorothiazide, HCTZ: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Amiloride; Hydrochlorothiazide, HCTZ: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Amlodipine; Atorvastatin: Atorvastatin, lovastatin, and simvastatin are HMG-CoA reductase inhibitors (statins) recognized as substrates and inhibitors of the P-glycoprotein (P-gp) transport system. Likewise, studies show that lansoprazole, omeprazole, and pantoprazole are also substrates and inhibitors of P-gp. Due to competitive inhibition of the P-gp transport system, coadministration may lead to increased intestinal absorption and/or decreased hepatic excretion of either product. The resulting increased drug bioavailability could lead to increased adverse events, including serious myopathies in the case of higher than normal statin plasma concentrations. For example, P-gp inhibition was suspected in a case report involving a patient presenting to the emergency room with rhabdomyolysis, causing third-degree AV block. The patient's medication history included atorvastatin (> 1 year history), esomeprazole (6-week history), and clarithromycin (500 mg x 3 doses prior to admission). Symptoms of weakness, shortness of breath, and chest pain coincided with the start of esomeprazole therapy. Due to the timing of symptom onset, clinicians suspected that esomeprazole likely increased atorvastatin plasma concentrations leading to rhabdomyolysis and further complications. Although competitive inhibition of CYP isoenzyme metabolism could have played a minor role in the interaction, the main pathway was thought to be competitive P-gp inhibition. Caution is therefore warranted when combining atorvastatin, lovastatin, red yeast rice (structurally similar to lovastatin), or simvastatin with esomeprazole, lansoprazole, omeprazole, or pantoprazole. Substituting with dexlansoprazole or rabeprazole may represent a safer alternative. Treatment with pravastatin, fluvastatin, and rosuvastatin may also decrease the risk of a P-gp interaction.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Amobarbital: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Amphetamine: Patients receiving amphetamine; dextroamphetamine or extended-release amphetamine; dextroamphetamine with a proton pump inhibitor should be monitored for changes in clinical efficacy. Proton pump inhibitors (PPIs) may alter the pharmacokinetics of amphetamine; dextroamphetamine due to a reduction in gastric acidity. An interaction has been noted with the extended-release product (Adderall XR) when administered with a PPI. Co-administration of Adderall XR 20 mg and omeprazole 40 mg resulted in a decrease in median Tmax of d-amphetamine and l-amphetamine by 1.25 hours and 2.5 hours, respectively, compared to administration of Adderall XR alone.The AUC and maximal concentration (Cmax) of each moiety were unaffected.
    Amphetamine; Dextroamphetamine Salts: Patients receiving amphetamine; dextroamphetamine or extended-release amphetamine; dextroamphetamine with a proton pump inhibitor should be monitored for changes in clinical efficacy. Proton pump inhibitors (PPIs) may alter the pharmacokinetics of amphetamine; dextroamphetamine due to a reduction in gastric acidity. An interaction has been noted with the extended-release product (Adderall XR) when administered with a PPI. Co-administration of Adderall XR 20 mg and omeprazole 40 mg resulted in a decrease in median Tmax of d-amphetamine and l-amphetamine by 1.25 hours and 2.5 hours, respectively, compared to administration of Adderall XR alone.The AUC and maximal concentration (Cmax) of each moiety were unaffected.
    Amphetamine; Dextroamphetamine: Patients receiving amphetamine; dextroamphetamine or extended-release amphetamine; dextroamphetamine with a proton pump inhibitor should be monitored for changes in clinical efficacy. Proton pump inhibitors (PPIs) may alter the pharmacokinetics of amphetamine; dextroamphetamine due to a reduction in gastric acidity. An interaction has been noted with the extended-release product (Adderall XR) when administered with a PPI. Co-administration of Adderall XR 20 mg and omeprazole 40 mg resulted in a decrease in median Tmax of d-amphetamine and l-amphetamine by 1.25 hours and 2.5 hours, respectively, compared to administration of Adderall XR alone.The AUC and maximal concentration (Cmax) of each moiety were unaffected.
    Ampicillin: Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.
    Ampicillin; Sulbactam: Proton pump inhibitors (PPIs) have long-lasting effects on the secretion of gastric acid. For enteral ampicillin, whose bioavailability is influenced by gastric pH, the concomitant administration of PPIs can exert a significant effect on ampicillin absorption.
    Anticholinergics: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Aprepitant, Fosaprepitant: Use caution if lansoprazole and aprepitant, fosaprepitant are used concurrently and monitor for an increase in lansoprazole-related adverse effects for several days after administration of a multi-day aprepitant regimen. Lansoprazole is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of lansoprazole. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Aspirin, ASA; Butalbital; Caffeine: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Atazanavir: Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%.
    Atazanavir; Cobicistat: Coadministration of proton pump inhibitors (PPIs) with atazanavir in treatment-experienced patients is contraindicated. PPIs can be used with atazanavir in treatment-naive patients under specific administration restrictions. In treatment-naive patients >= 40 kg, the PPI dose should not exceed the equivalent of omeprazole 20 mg/day, and the PPI must be administered 12 hours before atazanavir and ritonavir; use the dosage regimen of atazanavir 300 mg boosted with ritonavir 100 mg given once daily with food. While data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant PPIs, the same recommendations regarding timing and maximum doses of concomitant PPIs should be followed. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with a PPI. A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Additionally, after multiple doses of omeprazole (40 mg/day) and atazanavir (400 mg/day, 2 hours after omeprazole) without ritonavir, the AUC of atazanavir was decreased by 94%, Cmax by 96%, and Cmin by 95%. Use caution when administering cobicistat and lansoprazole concurrently. Cobicistat is an inhibitor of CYP3A and P-glycoprotein (P-gp). Coadministration of cobicistat with CYP3A and P-gp substrates, such as lansoprazole, can increase lansoprazole exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Atenolol; Chlorthalidone: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Atorvastatin: Atorvastatin, lovastatin, and simvastatin are HMG-CoA reductase inhibitors (statins) recognized as substrates and inhibitors of the P-glycoprotein (P-gp) transport system. Likewise, studies show that lansoprazole, omeprazole, and pantoprazole are also substrates and inhibitors of P-gp. Due to competitive inhibition of the P-gp transport system, coadministration may lead to increased intestinal absorption and/or decreased hepatic excretion of either product. The resulting increased drug bioavailability could lead to increased adverse events, including serious myopathies in the case of higher than normal statin plasma concentrations. For example, P-gp inhibition was suspected in a case report involving a patient presenting to the emergency room with rhabdomyolysis, causing third-degree AV block. The patient's medication history included atorvastatin (> 1 year history), esomeprazole (6-week history), and clarithromycin (500 mg x 3 doses prior to admission). Symptoms of weakness, shortness of breath, and chest pain coincided with the start of esomeprazole therapy. Due to the timing of symptom onset, clinicians suspected that esomeprazole likely increased atorvastatin plasma concentrations leading to rhabdomyolysis and further complications. Although competitive inhibition of CYP isoenzyme metabolism could have played a minor role in the interaction, the main pathway was thought to be competitive P-gp inhibition. Caution is therefore warranted when combining atorvastatin, lovastatin, red yeast rice (structurally similar to lovastatin), or simvastatin with esomeprazole, lansoprazole, omeprazole, or pantoprazole. Substituting with dexlansoprazole or rabeprazole may represent a safer alternative. Treatment with pravastatin, fluvastatin, and rosuvastatin may also decrease the risk of a P-gp interaction.
    Atorvastatin; Ezetimibe: Atorvastatin, lovastatin, and simvastatin are HMG-CoA reductase inhibitors (statins) recognized as substrates and inhibitors of the P-glycoprotein (P-gp) transport system. Likewise, studies show that lansoprazole, omeprazole, and pantoprazole are also substrates and inhibitors of P-gp. Due to competitive inhibition of the P-gp transport system, coadministration may lead to increased intestinal absorption and/or decreased hepatic excretion of either product. The resulting increased drug bioavailability could lead to increased adverse events, including serious myopathies in the case of higher than normal statin plasma concentrations. For example, P-gp inhibition was suspected in a case report involving a patient presenting to the emergency room with rhabdomyolysis, causing third-degree AV block. The patient's medication history included atorvastatin (> 1 year history), esomeprazole (6-week history), and clarithromycin (500 mg x 3 doses prior to admission). Symptoms of weakness, shortness of breath, and chest pain coincided with the start of esomeprazole therapy. Due to the timing of symptom onset, clinicians suspected that esomeprazole likely increased atorvastatin plasma concentrations leading to rhabdomyolysis and further complications. Although competitive inhibition of CYP isoenzyme metabolism could have played a minor role in the interaction, the main pathway was thought to be competitive P-gp inhibition. Caution is therefore warranted when combining atorvastatin, lovastatin, red yeast rice (structurally similar to lovastatin), or simvastatin with esomeprazole, lansoprazole, omeprazole, or pantoprazole. Substituting with dexlansoprazole or rabeprazole may represent a safer alternative. Treatment with pravastatin, fluvastatin, and rosuvastatin may also decrease the risk of a P-gp interaction.
    Atropine: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Atropine; Difenoxin: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Atropine; Diphenoxylate: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Atropine; Edrophonium: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy. The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Axitinib: Monitor patients for increased axitinib-related adverse events if coadministration with lansoprazole occurs. Axitinib is primarily metabolized by CYP3A4, and to a lesser extent by CYP1A2, CYP2C19, and UGT1A1. Lansoprazole is a CYP2C19 inhibitor. Theoretically, exposure to axitinib may be increased. While the aqueous solubility of axitinib is pH dependent, with higher pH resulting in lower solubility, this effect was not significant when studied with rabeprazole; dosage adjustments are not recommended with proton pump inhibitors.
    Azilsartan; Chlorthalidone: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Azithromycin: Both lansoprazole and azithromycin are P-glycoprotein (PGP) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Barbiturates: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy. The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Belladonna; Opium: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Benazepril; Hydrochlorothiazide, HCTZ: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Bendroflumethiazide; Nadolol: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Benztropine: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Bisacodyl: The concomitant use of bisacodyl oral tablets with drugs that raise gastric pH like proton pump inhibitors can cause the enteric coating of the bisacodyl tablets to dissolve prematurely, leading to possible gastric irritation or dyspepsia. When taking bisacodyl tablets, it is advisable to avoid PPIs within 1 hour before or after the bisacodyl dosage.
    Bisoprolol; Hydrochlorothiazide, HCTZ: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Boceprevir: Close clinical monitoring is advised when administering lansoprazole with boceprevir due to an increased potential for lansoprazole-related adverse events. If lansoprazole dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of lansoprazole. Lansoprazole is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated lansoprazole plasma concentrations.
    Bortezomib: Bortezomib may inhibit CYP2C19 activity at therapeutic concentrations and increase exposure to drugs that are substrates for this enzyme including proton pump inhibitors.
    Bosentan: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Bosentan induces hepatic cytochrome P-450 enzyme CYP3A4, one enzyme responsible for the metabolism of some PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If bosentan and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Bosutinib: Bosutinib displays pH-dependent aqueous solubility. Concomitant use of bosutinib and lansoprazole resulted in decreased plasma exposure of bosutinib. Consider using a short-acting antacid or H2 blocker if acid suppression therapy is needed; separate the administration of bosutinib and antacids or H2-blockers by more than 2 hours. In a cross-over trial in 24 healthy volunteers, the Cmax and AUC values of bosutinib were decreased by 46% and 26%, respectively, following a single oral dose of bosutinib 400 mg administered after multiple oral doses of lansoprazole 60 mg. Additionally, bosutinib may increase the plasma concentration of P-gp substrates such as, lansoprazole.
    Budesonide: Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
    Budesonide; Formoterol: Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
    Bumetanide: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Butabarbital: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Cabozantinib: Monitor for an increase in lansoprazole-related adverse events if concomitant use with cabozantinib is necessary, as plasma concentrations of lansoprazole may be increased. Cabozantinib is a P-glycoprotein (P-gp) inhibitor and lansoprazole is a substrate of P-gp; the clinical relevance of this finding is unknown.
    Calcium Carbonate; Risedronate: Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
    Canagliflozin: Canagliflozin is a substrate/weak inhibitor of drug transporter P glycoprotein (P-gp). Lansoprazole is a PGP inhibitor/substrate. Theoretically, concentrations of either drug may be increased. Patients should be monitored for changes in glycemic control and possible adverse reactions.
    Canagliflozin; Metformin: Canagliflozin is a substrate/weak inhibitor of drug transporter P glycoprotein (P-gp). Lansoprazole is a PGP inhibitor/substrate. Theoretically, concentrations of either drug may be increased. Patients should be monitored for changes in glycemic control and possible adverse reactions.
    Candesartan; Hydrochlorothiazide, HCTZ: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Captopril; Hydrochlorothiazide, HCTZ: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Carbamazepine: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Carbamazepine induces hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If carbamazepine and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Carvedilol: Altered concentrations of lansoprazole and/or carvedilol may occur during coadministration. Carvedilol and lansoprazole are both substrates and inhibitors of P-glycoprotein (P-gp). Use caution if concomitant use is necessary and monitor for increased side effects.
    Cefpodoxime: Cefpodoxime proxetil requires a low gastric pH for dissolution; therefore, concurrent administration with medications that increase gastric pH, such as proton pump inhibitors (PPIs) may decrease the bioavailability of cefpodoxime. When cefpodoxime was administered with high doses of antacids and H2-blockers, peak plasma concentrations were reduced by 24% and 42% and the extent of absorption was reduced by 27% and 32%, respectively. The rate of absorption is not affected.
    Ceftibuten: Coadministration of 150 mg of ranitidine every 12 hours for 3 days increased the ceftibuten Cmax by 23 percent and ceftibuten AUC by 16 percent. Based on this information, increased gastric pH caused by PPIs may possibly affect the kinetics of ceftibuten.
    Cefuroxime: Avoid the concomitant use of proton pump inhibitors (PPIs) and cefuroxime. Drugs that reduce gastric acidity, such as PPIs, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Ceritinib: Use caution if coadministration of ceritinib with Lansoprazole is necessary, as the bioavailability of ceritinib may be reduced. Ceritinib displays pH-dependent solubility with decreased solubility at a higher pH, but data are conflicting regarding clinical significance. In healthy subjects, the AUC and Cmax of ceritinib decreased by 76% and 79%, respectively, when a single dose was administered with esomeprazole. However, in a subgroup of patients with NSCLC from a multicenter, open-label clinical trial, the AUC and Cmax of ceritinib decreased by 30% and 25%, respectively, after a single dose was administered with proton pump inhibitors; there was no clinically meaningful effect on ceritinib exposure at steady state.
    Chlordiazepoxide; Clidinium: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Chlorothiazide: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Chlorthalidone: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Chlorthalidone; Clonidine: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Citalopram: The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with lansoprazole, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Clobazam: A dosage reduction of clobazam may be necessary during co-administration of lansoprazole. Metabolism of N-desmethylclobazam, the active metabolite of clobazam, occurs primarily through CYP2C19 and lansoprazole is an inhibitor of CYP2C19 in vitro. Extrapolation from pharmacogenomic data indicates that concurrent use of clobazam with moderate or potent inhibitors of CYP2C19 may result in up to a 5-fold increase in exposure to N-desmethylclobazam. Adverse effects, such as sedation, lethargy, ataxia, or insomnia may be potentiated.
    Clopidogrel: Use clopidogrel and lansoprazole together with caution as it may reduce the antiplatelet activity of clopidogrel when given concomitantly or 12 hours apart. The American College of Cardiology Foundation (ACCF), American College of Gastroenterology (ACG) and American Heart Association (AHA) state that routine use of proton pump inhibitor (PPI) therapy is not recommended for patients at lower risk of gastrointestinal bleed but should be considered in those at high risk, such as those with a history of gastrointestinal bleed. Clinicians should carefully assess the risks and benefits of PPI use in patients on clopidogrel therapy and administration should be based on clinical need. If necessary, consider using a PPI medication with less pronounced effects on antiplatelet activity, such as lansoprazole; omeprazole and esomeprazole should be avoided. Clopidogrel requires hepatic biotransformation via 2 cytochrome dependent oxidative steps; the CYP2C19 isoenzyme is involved in both steps. All PPIs are CYP219 substrates, and, to varying extents, are also inhibitors; thus, it is possible that any PPI may decrease the conversion of clopidogrel to its active metabolite, thereby reducing its effectiveness.
    Cobicistat: Use caution when administering cobicistat and lansoprazole concurrently. Cobicistat is an inhibitor of CYP3A and P-glycoprotein (P-gp). Coadministration of cobicistat with CYP3A and P-gp substrates, such as lansoprazole, can increase lansoprazole exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: Use caution when administering cobicistat and lansoprazole concurrently. Cobicistat is an inhibitor of CYP3A and P-glycoprotein (P-gp). Coadministration of cobicistat with CYP3A and P-gp substrates, such as lansoprazole, can increase lansoprazole exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as lansoprazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. Use caution when administering cobicistat and lansoprazole concurrently. Cobicistat is an inhibitor of CYP3A and P-glycoprotein (P-gp). Coadministration of cobicistat with CYP3A and P-gp substrates, such as lansoprazole, can increase lansoprazole exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Cobimetinib: If concurrent use of cobimetinib and lansoprazole is necessary, use caution and monitor for a possible increase in cobimetinib-related adverse effects. Cobimetinib is a P-glycoprotein (P-gp) substrate, and lansoprazole is a P-gp inhibitor; coadministration may result in increased cobimetinib exposure. However, coadministration of cobimetinib with another P-gp inhibitor, vemurafenib (960 mg twice daily), did not result in clinically relevant pharmacokinetic drug interactions.
    Conivaptan: Avoid coadministration of conivaptan, a CYP3A4/P-glycoprotein (P-gp) inhibitor and lansoprazole, a CYP3A4/P-gp substrate. Concurrent use may result in elevated lansoprazole serum concentrations. According to the manufacturer of conivaptan, concomitant use of conivaptan, a strong CYP3A4 inhibitor, and CYP3A substrates, such as lansoprazole, should be avoided. Coadministration of conivaptan with other CYP3A substrates (midazolam, simvastatin, amlodipine) has resulted in increased mean AUC values (2 to 3 times). Theoretically, similar pharmacokinetic effects could be seen with lansoprazole. Treatment with lansoprazole may be initiated no sooner than 1 week after completion of conivaptan therapy.
    Crizotinib: Drugs that elevate the gastric pH, such as proton pump inhibitors (PPIs), may decrease the solubility of crizotinib and subsequently reduce its bioavailability. The aqueous solubility of crizotinib is pH dependent, with higher pH resulting in lower solubility. Formal studies have not been conducted. Also, concomitant use of crizotinib and some PPIs (dexlansoprazole, esomeprazole, rabeprazole, lansoprazole, omeprazole, pantoprazole) may result in increased concentrations of the PPIs. Crizotinib is a CYP3A4 and P-glycoprotein (PGP) inhibitor, while dexlansoprazole, esomeprazole, and rabeprazole are CYP3A4 substrates. Lansoprazole and omeprazole are CYP3A4 substrates and a PGP substrates/inhibitors, which may also result in increased crizotinib concentrations. Pantoprazole is a CYP3A4 substrate/inhibitor and a PGP substrate/inhibitor. Monitor patients for toxicity with coadministration.
    Cyanocobalamin, Vitamin B12: Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency.
    Cyclophosphamide: Use caution if cyclophosphamide is used concomitantly with lansoprazole, and monitor for possible changes in the efficacy or toxicity profile of cyclophosphamide. The clinical significance of this interaction is unknown. Cyclophosphamide is a prodrug that is hydroxylated and activated primarily by CYP2B6; the contribution of CYP3A4 to the activation of cyclophosphamide is variable. Additional isoenzymes involved in the activation of cyclophosphamide include CYP2A6, 2C9, 2C18, and 2C19. N-dechloroethylation to therapeutically inactive but neurotoxic metabolites occurs primarily via CYP3A4. The active metabolites, 4-hydroxycyclophosphamide and aldophosphamide, are then inactivated by aldehyde dehydrogenase-mediated oxidation. Lansoprazole is a moderate in vitro CYP2C9 and 2C19 inhibitor; conversion of cyclophosphamide to its active metabolites may be affected. In vitro, coadministration with troleandomycin, a CYP3A4 inhibitor, had little-to-no effect on cyclophosphamide metabolism. However, concurrent use of cyclophosphamide conditioning therapy with itraconazole (a strong CYP3A4 inhibitor) and fluconazole (a moderate CYP3A4 inhibitor) in a randomized trial resulted in increases in serum bilirubin and creatinine, along with increased exposure to toxic cyclophosphamide metabolites (n = 197).
    Cysteamine: Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with proton pump inhibitors (PPIs). Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. Concomitant administration of omeprazole 20 mg did not alter the pharmacokinetics of delayed-release cysteamine when administered with orange juice; however, the effect of omeprazole on the pharmacokinetics of delayed-release cysteamine when administered with water have not been studied.
    Dabigatran: Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with lansoprazole, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like lansoprazole in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with lansoprazole, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
    Dabrafenib: Proton pump inhibitors (PPIs) elevate the gastric pH and may alter the solubility of dabrafenib. Therefore, the concomitant use of dabrafenib and PPIs may reduce the systemic exposure and bioavailability of dabrafenib. No formal trials have been performed to evaluate this interaction and it is not known how this interaction affects the efficacy of dabrafenib.
    Daclatasvir: Systemic exposure of lansoprazole, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of lansoprazole; monitor patients for potential adverse effects.
    Darifenacin: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Darunavir; Cobicistat: Use caution when administering cobicistat and lansoprazole concurrently. Cobicistat is an inhibitor of CYP3A and P-glycoprotein (P-gp). Coadministration of cobicistat with CYP3A and P-gp substrates, such as lansoprazole, can increase lansoprazole exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: Caution is advised when administering lansoprazole concurrently with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir. Use of these drugs together may result elevated concentrations lansoprazole, paritaprevir, ritonavir, dasabuvir and ombitasvir. Predications regarding this interaction can be made based on the drugs metabolic pathways. Lansoprazole is a substrate of CYP3A4 and a substrate/inhibitor of P-glycoprotein (P-gp). Ritonavir is an inhibitor/substrate of CYP3A4 and a P-gp substrate. Paritaprevir, dasabuvir, and ombitasvir are substrates of P-gp. Monitor for adverse reactions. Caution is advised when administering lansoprazole concurrently with dasabuvir; ombitasvir; paritaprevir; ritonavir. Use of these drugs together may result elevated concentrations of lansoprazole, paritaprevir, ritonavir, dasabuvir and ombitasvir. Predications regarding this interaction can be made based on the drugs metabolic pathways. Lansoprazole is a substrate of CYP3A4 and a substrate/inhibitor of P-glycoprotein (P-gp). Ritonavir is an inhibitor/substrate of CYP3A4 and a P-gp substrate. Paritaprevir, dasabuvir, and ombitasvir are substrates of P-gp. Monitor for adverse reactions. Use caution when administering ritonavir and lansoprazole concurrently. Ritonavir is an inhibitor of CYP3A and P-glycoprotein (P-gp). Coadministration of ritonavir with CYP3A and P-gp substrates, such as lansoprazole, can increase lansoprazole exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Dasatinib: Although not specifically studied, long-term suppression of gastric acid secretion by proton pump inhibitors (PPIs) is also likely to decrease the exposure to dasatinib. The concomitant use these agents is not recommended. For example, in a study of 24 healthy subjects, administration of a single 50 mg dose of dasatinib 10 hours after famotidine reduced the AUC and Cmax of dasatinib by 61% and 63%, respectively. Because separating the administration of dasatinib and antacids by at least 2 hours minimizes the interaction, the use of antacids should be considered in place of PPIs in patients receiving dasatinib therapy.
    Delavirdine: Because proton pump inhibitors (PPIs) increase gastric pH, decreased delavirdine absorption may occur. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of PPIs with delavirdine is not recommended.
    Dexamethasone: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Dexamethasone induces hepatic cytochrome P-450 enzyme CYP3A4, one enzyme responsible for the metabolism of some PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If dexamethasone and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Dexmethylphenidate: The effects of gastrointestinal pH alterations on the absorption of methylphenidate extended release capsules (Ritalin LA) and dexmethylphenidate extended-release tablets (Focalin XR) have not been studied. Although the SODAS system (drug delivery system utilized in Ritalin LA and Focalin XR) is thought to be minimally affected by changes in pH, per the manufacturer, the modified release characteristics of both extended-release formulations are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of dexmethylphenidate or methylphenidate. Patients receiving these extended-release products (Focalin XR or Ritalin LA) with acid suppressants should be monitored for adverse effects and therapeutic efficacy.
    Dextroamphetamine: Patients receiving amphetamine; dextroamphetamine or extended-release amphetamine; dextroamphetamine with a proton pump inhibitor should be monitored for changes in clinical efficacy. Proton pump inhibitors (PPIs) may alter the pharmacokinetics of amphetamine; dextroamphetamine due to a reduction in gastric acidity. An interaction has been noted with the extended-release product (Adderall XR) when administered with a PPI. Co-administration of Adderall XR 20 mg and omeprazole 40 mg resulted in a decrease in median Tmax of d-amphetamine and l-amphetamine by 1.25 hours and 2.5 hours, respectively, compared to administration of Adderall XR alone.The AUC and maximal concentration (Cmax) of each moiety were unaffected.
    Diclofenac: If possible, avoid concurrent use of diclofenac with inhibitors of CYP2C9, such as lansoprazole; if coadministration is required, do not exceed a total daily diclofenac dose of 100 mg. When used with a CYP2C9 inhibitor the systemic exposure to diclofenac (a CYP2C9 substrate) may increase, potentially resulting in adverse events.
    Diclofenac; Misoprostol: If possible, avoid concurrent use of diclofenac with inhibitors of CYP2C9, such as lansoprazole; if coadministration is required, do not exceed a total daily diclofenac dose of 100 mg. When used with a CYP2C9 inhibitor the systemic exposure to diclofenac (a CYP2C9 substrate) may increase, potentially resulting in adverse events. The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents including misoprostol. Proton pump inhibitors inhibit only actively secreting H+-pumps.
    Dicyclomine: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Digoxin: Lansoprazole or other proton pump inhibitors (PPIs) can affect digoxin absorption due to their long-lasting effect on gastric acid secretion. Additionally, PPIs may slightly increase digoxin bioavailability. Patients with digoxin serum levels at the upper end of the therapeutic range may need to be monitored for potential increases in serum digoxin levels when a PPI is coadministered with digoxin. Finally, PPIs have been associated with hypomagnesemia. Becuase, low serum magnesium may lead to irregular heartbeat and increase the likelihood of serious cardiac arrhythmias, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and digoxin concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Doxorubicin: Lansoprazole is a P-glycoprotein (P-gp) inhibitor and doxorubicin is a major P-gp substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of lansoprazole and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Dronabinol, THC: Use caution if coadministration of dronabinol with lansoprazole is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; lansoprazole is a moderate inhibitor of CYP2C9 in vitro. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Dronedarone: Dronedarone is metabolized by and is an inhibitor of CYP3A. Lansoprazole is a substrate for CYP3A4. The concomitant administration of dronedarone and CYP3A substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution.
    Edoxaban: Coadministration of edoxaban and lansoprazole may result in increased concentrations of edoxaban. Edoxaban is a P-glycoprotein (P-gp) substrate and lansoprazole is a P-gp inhibitor. Increased concentrations of edoxaban may occur during concomitant use of lansoprazole; monitor for increased adverse effects of edoxaban. Dosage reduction may be considered for patients being treated for deep venous thrombosis (DVT) or pulmonary embolism.
    Efavirenz; Emtricitabine; Tenofovir: Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as lansoprazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Eliglustat: Coadministration of lansoprazole and eliglustat may result in increased plasma concentrations of lansoprazole. Monitor patients closely for lansoprazole-related adverse effects; if appropriate, consider reducing the lansoprazole dosage and titrating to clinical effect. Lansoprazole is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine. Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as lansoprazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Emtricitabine; Tenofovir disoproxil fumarate: Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as lansoprazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Enalapril; Hydrochlorothiazide, HCTZ: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Eprosartan; Hydrochlorothiazide, HCTZ: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Erlotinib: Avoid coadministration of lansoprazole with erlotinib if possible due to the risk of decreased efficacy of erlotinib. Erlotinib solubility is pH dependent and solubility decreases as pH increases. Coadministration of erlotinib with medications that increase the pH of the upper gastrointestinal tract, like proton pump inhibitors (PPIs), may decrease the absorption of erlotinib. Concomitant use of erlotinib and omeprazole, a PPI, decreased erlotinib AUC and Cmax by 46% and 61% respectively. Increasing the dose of erlotinib may not compensate for the loss of exposure. Proton-pump inhibitors exert their effect over an extended amount of time, as a result spacing of doses is also not expected to eliminate the interaction. Substitution of antacids, separated from the erlotinib dose by several hours, may be considered. No formal analysis has been performed to assess the impact of antacids on erlotinib pharmacokinetics.
    Escitalopram: The plasma concentration of escitalopram, a CYP2C19 substrate, may be increased when administered concurrently with lansoprazole, a CYP2C19 inhibitor. If these drugs are used together, monitor for escitalopram-associated adverse reactions.
    Eslicarbazepine: Eslicarbazepine may inhibit the CYP2C19-mediated and induce the CYP3A4-mediated metabolism of lansoprazole; both enzymes are involved in the metabolism of proton pump inhibitors (PPIs). It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and PPIs. If eslicarbazepine and PPI must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy, or for signs of PPI side effects.
    Ethacrynic Acid: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Etoposide, VP-16: Monitor for an increased incidence of etoposide-related adverse effects if used concomitantly with lansoprazole. Lansoprazole is an inhibitor of P-glycoprotein (P-gp) and etoposide, VP-16 is a P-gp substrate. Coadministration may increase etoposide concentrations.
    Ezetimibe; Simvastatin: Atorvastatin, lovastatin, and simvastatin are HMG-CoA reductase inhibitors (statins) recognized as substrates and inhibitors of the P-glycoprotein (P-gp) transport system. Likewise, studies show that lansoprazole, omeprazole, and pantoprazole are also substrates and inhibitors of P-gp. Due to competitive inhibition of the P-gp transport system, coadministration may lead to increased intestinal absorption and/or decreased hepatic excretion of either product. The resulting increased drug bioavailability could lead to increased adverse events, including serious myopathies in the case of higher than normal statin plasma concentrations. For example, P-gp inhibition was suspected in a case report involving a patient presenting to the emergency room with rhabdomyolysis, causing third-degree AV block. The patient's medication history included atorvastatin (> 1 year history), esomeprazole (6-week history), and clarithromycin (500 mg x 3 doses prior to admission). Symptoms of weakness, shortness of breath, and chest pain coincided with the start of esomeprazole therapy. Due to the timing of symptom onset, clinicians suspected that esomeprazole likely increased atorvastatin plasma concentrations leading to rhabdomyolysis and further complications. Although competitive inhibition of CYP isoenzyme metabolism could have played a minor role in the interaction, the main pathway was thought to be competitive P-gp inhibition. Caution is therefore warranted when combining atorvastatin, lovastatin, red yeast rice (structurally similar to lovastatin), or simvastatin with esomeprazole, lansoprazole, omeprazole, or pantoprazole. Substituting with dexlansoprazole or rabeprazole may represent a safer alternative. Treatment with pravastatin, fluvastatin, and rosuvastatin may also decrease the risk of a P-gp interaction.
    Fenofibric Acid: At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as lansoprazole, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of lansoprazole during coadministration with fenofibric acid.
    Fesoterodine: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Flavoxate: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Flibanserin: The concomitant use of flibanserin and strong CYP2C19 inhibitors, such as proton pump inhibitors (PPIs), may increase flibanserin concentrations, resulting in severe hypotension, syncope, and/or CNS depression. Therefore, patients should be monitored for flibanserin-induced adverse reactions, and the risks of combination therapy should be discussed with the patient. In addition, the concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including pantoprazole, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions.
    Fluvoxamine: Fluvoxamine is a major inhibitor of the cytochrome P450 enzyme 2C19. Several proton pump inhibitors, including lansoprazole, are primary substrates of the CYP2C19 enzyme. Reduced metabolism and resulting elevated plasma concentrations of these PPIs may occur if combined with fluvoxamine. Monitor patients for PPI toxicity, such as headache or GI distress if these drugs are combined.
    Food: Administer on an empty stomach, 30 to 60 minutes before meals. If given once daily, administer before the first meal of the day. Antacids were used concomitantly with lansoprazole in clinical trials.
    Fosinopril; Hydrochlorothiazide, HCTZ: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Furosemide: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Gefitinib: If possible, avoid the concomitant use of gefitinib with lansoprazole. If coadministration is necessary, give gefitinib 12 hours after the last dose or 12 hours before the next dose of lansoprazole. Drugs that increase gastric pH may decrease plasma concentrations of gefitinib; coadministration of high doses of ranitidine with sodium bicarbonate (to maintain the gastric pH above 5) to healthy subjects decreased mean gefitinib AUC by 47%.
    Glycopyrrolate: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Glycopyrrolate; Formoterol: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Homatropine; Hydrocodone: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Hydantoins: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Phenytoin induces hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If phenytoin and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Hydralazine; Hydrochlorothiazide, HCTZ: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Irbesartan: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Lisinopril: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Losartan: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Methyldopa: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Metoprolol: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Moexipril: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Olmesartan: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Propranolol: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Quinapril: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Spironolactone: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Telmisartan: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Triamterene: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hydrochlorothiazide, HCTZ; Valsartan: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Hyoscyamine: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Idelalisib: Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with lansoprazole, a CYP3A substrate, as lansoprazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Indacaterol; Glycopyrrolate: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Iron: The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Isavuconazonium: Concomitant use of isavuconazonium with lansoprazole may result in increased serum concentrations of lansoprazole. Lansoprazole is a substrate of the hepatic isoenzyme CYP3A4 and the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If rifampin and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Isoniazid, INH; Rifampin: Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If rifampin and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Itraconazole: Itraconazole oral bioavailability requires an acidic environment for solubility. Proton pump inhibitors (PPIs) have been shown to reduce plasma concentrations of itraconazole. The interaction with antacids may be avoided by staggering the administration time with itraconazole. However, due to the sustained action of proton pump inhibitors (PPIs), a drug interaction may still occur even if administration times are adjusted. Proton pump inhibitors (PPIs) should be withheld or avoided in patients requiring oral itraconazole therapy.
    Ivacaftor: Use caution when administering ivacaftor and lansoprazole concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as lansoprazole, can increase lansoprazole exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Ketoconazole: Ketoconazole requires an acidic pH for absorption. Medications that increase gastric pH or decrease acid output can cause a notable decrease in the bioavailability of ketoconazole. Medications that have this effect are antacids, antimuscarinics, histamine H2-blockers, and proton pump inhibitors (PPIs). Except for antacids, these medications have a prolonged duration of action, and staggering their time of administration with ketoconazole by several hours may not prevent the drug interaction. An alternative imidazole antifungal should be chosen if any of these gastrointestinal medications are required. If these drugs must be coadministered, administer ketoconazole tablets with an acidic beverage and closely monitor for breakthrough infection.
    Ledipasvir; Sofosbuvir: Solubility of ledipasvir decreases as gastric pH increases; thus, coadministration of ledipasvir; sofosbuvir with proton pump inhibitors (PPIs) may result in lower ledipasvir plasma concentrations. Ledipasvir can be administered with PPIs if given simultaneously under fasting conditions. The PPI dose should not exceed a dose that is comparable to omeprazole 20 mg/day.
    Lesinurad: Use lesinurad and lansoprazole together with caution; lansoprazole may increase the systemic exposure of lesinurad. Lansoprazole is an inhibitor of CYP2C9 in vitro, and lesinurad is a CYP2C9 substrate.
    Loop diuretics: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Loperamide: The plasma concentrations of loperamide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with lansoprazole, a P-gp inhibitor. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
    Loperamide; Simethicone: The plasma concentrations of loperamide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with lansoprazole, a P-gp inhibitor. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
    Lopinavir; Ritonavir: Use caution when administering lopinavir; ritonavir and lansoprazole concurrently. Ritonavir is an inhibitor of CYP3A and P-glycoprotein (P-gp), while lopinavir is a P-gp inhibitor. Coadministration of lopinavir; ritonavir with CYP3A and P-gp substrates, such as lansoprazole, can increase lansoprazole exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined. Use caution when administering ritonavir and lansoprazole concurrently. Ritonavir is an inhibitor of CYP3A and P-glycoprotein (P-gp). Coadministration of ritonavir with CYP3A and P-gp substrates, such as lansoprazole, can increase lansoprazole exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Lovastatin: Atorvastatin, lovastatin, and simvastatin are HMG-CoA reductase inhibitors (statins) recognized as substrates and inhibitors of the P-glycoprotein (P-gp) transport system. Likewise, studies show that lansoprazole, omeprazole, and pantoprazole are also substrates and inhibitors of P-gp. Due to competitive inhibition of the P-gp transport system, coadministration may lead to increased intestinal absorption and/or decreased hepatic excretion of either product. The resulting increased drug bioavailability could lead to increased adverse events, including serious myopathies in the case of higher than normal statin plasma concentrations. For example, P-gp inhibition was suspected in a case report involving a patient presenting to the emergency room with rhabdomyolysis, causing third-degree AV block. The patient's medication history included atorvastatin (> 1 year history), esomeprazole (6-week history), and clarithromycin (500 mg x 3 doses prior to admission). Symptoms of weakness, shortness of breath, and chest pain coincided with the start of esomeprazole therapy. Due to the timing of symptom onset, clinicians suspected that esomeprazole likely increased atorvastatin plasma concentrations leading to rhabdomyolysis and further complications. Although competitive inhibition of CYP isoenzyme metabolism could have played a minor role in the interaction, the main pathway was thought to be competitive P-gp inhibition. Caution is therefore warranted when combining atorvastatin, lovastatin, red yeast rice (structurally similar to lovastatin), or simvastatin with esomeprazole, lansoprazole, omeprazole, or pantoprazole. Substituting with dexlansoprazole or rabeprazole may represent a safer alternative. Treatment with pravastatin, fluvastatin, and rosuvastatin may also decrease the risk of a P-gp interaction.
    Lovastatin; Niacin: Atorvastatin, lovastatin, and simvastatin are HMG-CoA reductase inhibitors (statins) recognized as substrates and inhibitors of the P-glycoprotein (P-gp) transport system. Likewise, studies show that lansoprazole, omeprazole, and pantoprazole are also substrates and inhibitors of P-gp. Due to competitive inhibition of the P-gp transport system, coadministration may lead to increased intestinal absorption and/or decreased hepatic excretion of either product. The resulting increased drug bioavailability could lead to increased adverse events, including serious myopathies in the case of higher than normal statin plasma concentrations. For example, P-gp inhibition was suspected in a case report involving a patient presenting to the emergency room with rhabdomyolysis, causing third-degree AV block. The patient's medication history included atorvastatin (> 1 year history), esomeprazole (6-week history), and clarithromycin (500 mg x 3 doses prior to admission). Symptoms of weakness, shortness of breath, and chest pain coincided with the start of esomeprazole therapy. Due to the timing of symptom onset, clinicians suspected that esomeprazole likely increased atorvastatin plasma concentrations leading to rhabdomyolysis and further complications. Although competitive inhibition of CYP isoenzyme metabolism could have played a minor role in the interaction, the main pathway was thought to be competitive P-gp inhibition. Caution is therefore warranted when combining atorvastatin, lovastatin, red yeast rice (structurally similar to lovastatin), or simvastatin with esomeprazole, lansoprazole, omeprazole, or pantoprazole. Substituting with dexlansoprazole or rabeprazole may represent a safer alternative. Treatment with pravastatin, fluvastatin, and rosuvastatin may also decrease the risk of a P-gp interaction.
    Luliconazole: Theoretically, luliconazole may increase the side effects of lansoprazole, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of lansoprazole, such as electroylyte changes. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 amd CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
    Lumacaftor; Ivacaftor: Lumacaftor; ivacaftor may reduce the efficacy of lansoprazole by substantially decreasing its systemic exposure. If used together, a lansoprazole dosage adjustment may be necessary to obtain the desired therapeutic effect. Lansoprazole is a CYP3A4 and CYP2C19 substrate; it is also a substrate and inhibitor of the P-glycoprotein (P-gp) transport system. Lumacaftor; ivacaftor is a strong inducer of CYP3A; in vitro data suggests is also has the potential to induce CYP2C19 and both induce and inhibit P-gp.
    Lumacaftor; Ivacaftor: Lumacaftor; ivacaftor may reduce the efficacy of lansoprazole by substantially decreasing its systemic exposure. If used together, a lansoprazole dosage adjustment may be necessary to obtain the desired therapeutic effect. Lansoprazole is a CYP3A4 and CYP2C19 substrate; it is also a substrate and inhibitor of the P-glycoprotein (P-gp) transport system. Lumacaftor; ivacaftor is a strong inducer of CYP3A; in vitro data suggests is also has the potential to induce CYP2C19 and both induce and inhibit P-gp. Use caution when administering ivacaftor and lansoprazole concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as lansoprazole, can increase lansoprazole exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Maraviroc: Use caution and closely monitor for increased adverse effects with the coadministration of maraviroc and lansoprazole as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); lansoprazole is an inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    Mefloquine: Proton pump inhibitors (PPIs) may increase plasma concentrations of mefloquine. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially patients with a neurological or psychiatric history.
    Mepenzolate: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Mephobarbital: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Mesalamine, 5-ASA: The dissolution of the coating on mesalamine extended-release capsules (Apriso) and the delayed-release tablets (Lialda) is dependent on pH. Avoid coadministration with drugs that raise gastric pH like proton pump inhibitors.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Methohexital: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Methotrexate: Use caution when administering high-dose methotrexate to patients receiving proton pump inhibitors (PPIs). Case reports and published population pharmacokinetic studies suggest that concomitant use of some PPIs such as omeprazole, pantoprazole, or esomeprazole with methotrexate primarily at high dose may elevate and prolong serum methotrexate concentrations and/or its metabolite hydroxymethotrexate, which may lead to methotrexate toxicities. In two of these cases, delayed methotrexate elimination was observed when high-dose methotrexate was coadministered with PPIs but was not observed when methotrexate was coadministered with ranitidine. However, no formal drug interaction studies of methotrexate with ranitidine have been conducted. Among adults who received high-dose methotrexate (median dose of 3500 mg/m2, range of 1000-5000 mg/m2), coadministration of PPIs such as omeprazole, lansoprazole, or rabeprazole was identified as a risk factor for delayed methotrexate elimination with an OR of 2.65 (95% confidence interval 1.036.82). The interaction may be partially explained by the inhibitory effects of PPIs on breast cancer resistance protein (BCRP, ABCG2) -mediated methotrexate transport. Altered methotrexate elimination may not be present or problematic among patients who receive lower methotrexate doses. For example, coadministration of lansoprazole 30 mg daily and naproxen 500 mg twice daily for 7 days to recipients of stable oral methotrexate doses (7.515 mg/week) for a minimum of 3 months did not alter the pharmacokinetic profile of either methotrexate or 7-hydroxymethotrexate. Specifically, the peak plasma concentration and area under the plasma concentration-time curve of methotrexate and 7-hydroxymethotrexate were within the 0.80 to 1.25 boundaries.
    Methscopolamine: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Methyclothiazide: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Methylphenidate: The effects of gastrointestinal pH alterations on the absorption of methylphenidate extended release capsules (Ritalin LA) and dexmethylphenidate extended-release tablets (Focalin XR) have not been studied. Although the SODAS system (drug delivery system utilized in Ritalin LA and Focalin XR) is thought to be minimally affected by changes in pH, per the manufacturer, the modified release characteristics of both extended-release formulations are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of dexmethylphenidate or methylphenidate. Patients receiving these extended-release products (Focalin XR or Ritalin LA) with acid suppressants should be monitored for adverse effects and therapeutic efficacy.
    Metolazone: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Misoprostol: The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents including misoprostol. Proton pump inhibitors inhibit only actively secreting H+-pumps.
    Mitotane: Use caution if mitotane and lansoprazole are used concomitantly, and monitor for decreased efficacy of lansoprazole and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and lansoprazole is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of lansoprazole.
    Modafinil: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Modafinil induces hepatic cytochrome P-450 enzyme CYP3A4 but significantly inhibits CYP2C19; both of these enzymes are responsible for the metabolism of PPIs. It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. If modafinil and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy, or for signs of PPI side effects.
    Mycophenolate: Concomitant administration of proton pump inhibitors (PPIs) with mycophenolate mofetil (Cellcept) appears to reduce MPA exposure AUC-12h (25.8 +/- 6.4 mg/L x h with omeprazole vs. 33.3 +/- 11.5 mg//L x h without omeprazole); however, the interaction does not appear to exist with mycophenolate sodium delayed-release tablets (Myfortic). Reduced systemic exposure of MPA after mycophenolate mofetil in the presence of a PPI appears to be due to impaired absorption of mycophenolate mofetil which may occur because of incomplete dissolution of mycophenolate mofetil in the stomach at elevated pH. The clinical significance of reduced MPA exposure is unknown; however patients should be evaluated periodically if mycophenolate mofetil is administered with a PPI. Of note, MPA concentrations appear to be reduced in the initial hours after mycophenolate mofetil receipt but increase later in the dosing interval because of enterohepatic recirculation. A second peak in the concentration-time profile of MPA is observed 612 hours after dosing due to enterohepatic recirculation. For example, the 12-hour plasma concentrations of MPA were similar among patients who received mycophenolate mofetil with or without omeprazole. The biphasic plasma concentration-time course of MPA due to extensive enterohepatic circulation hampers therapeutic drug monitoring of MPA. Drug exposure as measured by AUC-12h is the best estimator for the clinical effectiveness of mycophenolate, but measurement of full-dose interval MPA AUC-12h requires collection of multiple samples over a 12-hour period; MPA predose concentrations correlate poorly with MPA AUC-12h. The interaction does not appear to exist with Mycophenolate sodium (Myfortic).
    Nelfinavir: Use of proton pump inhibitors with nelfinavir is not recommended. Coadministration may result in decreased nelfinavir exposure, subtherapeutic antiretroviral activity, and possibility resistant HIV mutations. In one study, concurrent use of nelfinavir with omeprazole resulted in decreased nelfinavir AUC, Cmax, and Cmin by 36%, 37%, and 39%, respectively.
    Niacin; Simvastatin: Atorvastatin, lovastatin, and simvastatin are HMG-CoA reductase inhibitors (statins) recognized as substrates and inhibitors of the P-glycoprotein (P-gp) transport system. Likewise, studies show that lansoprazole, omeprazole, and pantoprazole are also substrates and inhibitors of P-gp. Due to competitive inhibition of the P-gp transport system, coadministration may lead to increased intestinal absorption and/or decreased hepatic excretion of either product. The resulting increased drug bioavailability could lead to increased adverse events, including serious myopathies in the case of higher than normal statin plasma concentrations. For example, P-gp inhibition was suspected in a case report involving a patient presenting to the emergency room with rhabdomyolysis, causing third-degree AV block. The patient's medication history included atorvastatin (> 1 year history), esomeprazole (6-week history), and clarithromycin (500 mg x 3 doses prior to admission). Symptoms of weakness, shortness of breath, and chest pain coincided with the start of esomeprazole therapy. Due to the timing of symptom onset, clinicians suspected that esomeprazole likely increased atorvastatin plasma concentrations leading to rhabdomyolysis and further complications. Although competitive inhibition of CYP isoenzyme metabolism could have played a minor role in the interaction, the main pathway was thought to be competitive P-gp inhibition. Caution is therefore warranted when combining atorvastatin, lovastatin, red yeast rice (structurally similar to lovastatin), or simvastatin with esomeprazole, lansoprazole, omeprazole, or pantoprazole. Substituting with dexlansoprazole or rabeprazole may represent a safer alternative. Treatment with pravastatin, fluvastatin, and rosuvastatin may also decrease the risk of a P-gp interaction.
    Nilotinib: Avoid the concomitant use of nilotinib and proton pump inhibitors (PPIs), as PPIs may cause a reduction in nilotinib bioavailability. Nilotinib displays pH-dependent solubility with decreased solubility at a higher pH. PPIs inhibit gastric acid secretion and elevate the gastric pH. Administration of a single 400-mg nilotinib dose with multiple oral doses of esomeprazole 40 mg/day reduced the nilotinib AUC by 34% in a study in healthy subjects. Increasing the dose is unlikely to compensate for the loss of nilotinib exposure; additionally, separating the administration of these agents may not eliminate the interaction as PPIs affect the pH of the upper GI tract for an extended period of time.
    Nintedanib: Lansoprazole is a moderate inhibitor of P-glycoprotein (P-gp) and nintedanib is a P-gp substrate. Coadministration may increase the concentration and clinical effect of nintedanib. If concomitant use of lansoprazole and nintedanib is necessary, closely monitor for increased nintedanib side effects including gastrointestinal toxicity, elevated liver enzymes, and hypertension. A dose reduction, interruption of therapy, or discontinuation of therapy may be necessary.
    Octreotide: The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents, such as octreotide. Proton pump inhibitors inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
    Olaparib: Use caution if coadministration of olaparib with lansoprazole is necessary, due to an increased risk of lansoprazole- and olaparib-related adverse reactions. Lansoprazole is a P-glycoprotein (P-gp) substrate / inhibitor. Olaparib is also an in vitro P-gp substrate / inhibitor, although the clinical relevance is unknown.
    Ombitasvir; Paritaprevir; Ritonavir: Caution is advised when administering lansoprazole concurrently with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir. Use of these drugs together may result elevated concentrations lansoprazole, paritaprevir, ritonavir, dasabuvir and ombitasvir. Predications regarding this interaction can be made based on the drugs metabolic pathways. Lansoprazole is a substrate of CYP3A4 and a substrate/inhibitor of P-glycoprotein (P-gp). Ritonavir is an inhibitor/substrate of CYP3A4 and a P-gp substrate. Paritaprevir, dasabuvir, and ombitasvir are substrates of P-gp. Monitor for adverse reactions. Use caution when administering ritonavir and lansoprazole concurrently. Ritonavir is an inhibitor of CYP3A and P-glycoprotein (P-gp). Coadministration of ritonavir with CYP3A and P-gp substrates, such as lansoprazole, can increase lansoprazole exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Oritavancin: Coadministration of oritavancin and lansoprazole may result in increases or decreases in lansoprazole exposure and may increase side effects or decrease efficacy of lansoprazole. Lansoprazole is metabolized by CYP3A4 and CYP2C19. Oritavancin weakly induces CYP3A4, while weakly inhibiting CYP2C19. If these drugs are administered concurrently, monitor the patient for signs of toxicity or lack of efficacy.
    Osimertinib: Use caution if coadministration of osimertinib and lansoprazole is necessary, due to the risk of increased osimertinib exposure. Lansoprazole is a P-glycoprotein inhibitor and osimertinib is an in vitro P-gp substrate. Coadministration may increase osimertinib-related adverse reactions.
    Oxcarbazepine: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Oxcarbazepine and its MHD metabolite induce hepatic cytochrome P-450 enzyme CYP3A4 but potently display dose-dependent CYP2C19 inhibition; both enzymes are involved in the metabolism of PPIs. It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. If oxcarbazepine and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy, or for signs of PPI side effects.
    Oxybutynin: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Pazopanib: Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours.
    Pentobarbital: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Phenobarbital: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Polyethylene Glycol; Electrolytes; Bisacodyl: The concomitant use of bisacodyl oral tablets with drugs that raise gastric pH like proton pump inhibitors can cause the enteric coating of the bisacodyl tablets to dissolve prematurely, leading to possible gastric irritation or dyspepsia. When taking bisacodyl tablets, it is advisable to avoid PPIs within 1 hour before or after the bisacodyl dosage.
    Ponatinib: Ponatinib displays pH-dependent aqueous solubility; therefore, concomitant use of ponatinib and proton-pump inhibitors, such as lansoprazole, may result in decreased bioavailability and plasma exposure of ponatinib. Avoid concomitant use of ponatinib with proton-pump inhibitors unless the benefit outweighs the possible risk of ponatinib underexposure. If the use of both agents is necessary, monitor patients for signs of reduced efficacy. Additionally, ponatinib may increase the plasma concentration of a P-gp substrate such as, lansoprazole.
    Posaconazole: The concurrent use of posaconazole oral suspension and proton pump inhibitors (PPIs) should be avoided, if possible, due to the potential for decreased posaconazole efficacy. If used in combination, closely monitor for breakthrough fungal infections. PPIs increase gastric pH, resulting in decreased posaconazole absorption and lower posaconazole plasma concentrations. When a single 400 mg dose of posaconazole oral suspension was administered with esomeprazole (40 mg PO daily), the mean reductions in Cmax were 46% and the mean reductions in AUC were 32% for posaconazole. The pharmacokinetics of posaconazole delayed-release tablets are not significantly affected by PPIs. Additionally, posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of many PPIs (dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole). Coadministration may result in increased plasma concentration of the PPIs.
    Primidone: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Propantheline: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Raltegravir: The manufacturer of raltegravir suggests that no dose adjustment for raltegravir is necessary when given concomitantly with agents that increase gastric pH. Coadministration of products that increase gastric pH, such as proton pump inhibitors (PPIs), may increase raltegravir concentrations due to increased raltegravir solubility at higher pH levels.The ratio of the AUC for raltegravir given with and without omeprazole was 3.12 (90% CI 2.13, 4.56).
    Red Yeast Rice: Caution is warranted when combining red yeast rice (structurally similar to lovastatin) with lansoprazole. Due to competitive inhibition of the P-gp transport system, coadministration may lead to increased intestinal absorption and/or decreased hepatic excretion of either product.
    Rifabutin: Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If rifampin and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Rifampin: Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If rifampin and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Rifamycins: Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If rifampin and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Rifapentine: Some manufacturers recommend avoiding the coadministration of rifampin and proton pump inhibitors (PPIs). Rifamycins induce multiple hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If rifampin and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Rifaximin: Although the clinical significance of this interaction is unknown, concurrent use of rifaximin, a P-glycoprotein (P-gp) substrate, and lansoprazole, a P-gp inhibitor, may substantially increase the systemic exposure to rifaximin; caution is advised if these drugs must be administered together. During one in vitro study, coadministration with cyclosporine, a potent P-gp inhibitor, resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC of rifaximin, respectively. In patients with hepatic impairment, the effects of reduced metabolism and P-gp inhibition may further increase exposure to rifaximin.
    Rilpivirine: Concurrent use of proton pump inhibitors and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Proton pump inhibitors inhibit secretion of gastric acid by proton pumps thereby increasing the gastric pH; for optimal absorption, rilpivirine requires an acidic environment. Coadministration of a proton pump inhibitor and rilpivirine may result in decreased rilpivirine absorption/serum concentrations, which could cause impaired virologic response to rilpivirine.
    Risedronate: Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
    Ritonavir: Use caution when administering ritonavir and lansoprazole concurrently. Ritonavir is an inhibitor of CYP3A and P-glycoprotein (P-gp). Coadministration of ritonavir with CYP3A and P-gp substrates, such as lansoprazole, can increase lansoprazole exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Rivaroxaban: Coadministration of rivaroxaban and lansoprazole may result in increases in rivaroxaban exposure and may increase bleeding risk. Lansoprazole is an inhibitor of P-gp, and rivaroxaban is a substrate of P-gp. If these drugs are administered concurrently, monitor the patient for signs and symptoms of bleeding.
    Sapropterin: Caution is advised with the concomitant use of sapropterin and lansoprazole as coadministration may result in increased systemic exposure of lansoprazole. Lansoprazole is a substrate for the drug transporter P-glycoprotein (P-gp); in vitro data show that sapropterin may inhibit P-gp. If these drugs are used together, closely monitor for increased side effects of lansoprazole.
    Saquinavir: Coadministration with omeprazole results in significantly increased saquinavir concentrations. A similar interaction is expected with all proton pump inhibitors (PPIs). If saquinavir must be administered with PPIs, the patient should be closely monitored for saquinavir-related toxicities, including gastrointestinal symptoms, increased triglycerides, and deep vein thrombosis (DVT). Coadministration with omeprazole results in significantly increased saquinavir concentrations. In a small study, 18 healthy individuals received saquinavir 1000 mg (with ritonavir 100 mg) twice daily for 15 days; on days 11 through 15 omeprazole 40 mg was given once daily, which resulted in an 82% increase in the saquinavir AUC. A similar interaction is expected with all PPIs.
    Scopolamine: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Secobarbital: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Secretin: Discontinue use of proton pump inhibitors before administering secretin. Patients who are receiving proton pump inhibitors at the time of stimulation testing may be hyperresponsive to secretin stimulation, falsely suggesting gastrinoma. The time required for serum gastrin concentrations to return to baseline after discontinuation of a proton pump inhibitor is specific to the individual drug.
    Simeprevir: Simeprevir, a P-glycoprotein (P-gp) and a mild intestinal CYP3A4 inhibitor, may increase the side effects of lansoprazole, which is a P-gp and CYP3A4 substrate. Additionally, increase side effects of simeprevir may occur as lansoprazole is a P-gp inhibitor and simeprevir is a P-gp substrate in vitro. Monitor patients for adverse effects of lansoprazole, such as electrolyte changes, and simeprevir, such as rash and phototoxicity.
    Simvastatin: Atorvastatin, lovastatin, and simvastatin are HMG-CoA reductase inhibitors (statins) recognized as substrates and inhibitors of the P-glycoprotein (P-gp) transport system. Likewise, studies show that lansoprazole, omeprazole, and pantoprazole are also substrates and inhibitors of P-gp. Due to competitive inhibition of the P-gp transport system, coadministration may lead to increased intestinal absorption and/or decreased hepatic excretion of either product. The resulting increased drug bioavailability could lead to increased adverse events, including serious myopathies in the case of higher than normal statin plasma concentrations. For example, P-gp inhibition was suspected in a case report involving a patient presenting to the emergency room with rhabdomyolysis, causing third-degree AV block. The patient's medication history included atorvastatin (> 1 year history), esomeprazole (6-week history), and clarithromycin (500 mg x 3 doses prior to admission). Symptoms of weakness, shortness of breath, and chest pain coincided with the start of esomeprazole therapy. Due to the timing of symptom onset, clinicians suspected that esomeprazole likely increased atorvastatin plasma concentrations leading to rhabdomyolysis and further complications. Although competitive inhibition of CYP isoenzyme metabolism could have played a minor role in the interaction, the main pathway was thought to be competitive P-gp inhibition. Caution is therefore warranted when combining atorvastatin, lovastatin, red yeast rice (structurally similar to lovastatin), or simvastatin with esomeprazole, lansoprazole, omeprazole, or pantoprazole. Substituting with dexlansoprazole or rabeprazole may represent a safer alternative. Treatment with pravastatin, fluvastatin, and rosuvastatin may also decrease the risk of a P-gp interaction.
    Simvastatin; Sitagliptin: Atorvastatin, lovastatin, and simvastatin are HMG-CoA reductase inhibitors (statins) recognized as substrates and inhibitors of the P-glycoprotein (P-gp) transport system. Likewise, studies show that lansoprazole, omeprazole, and pantoprazole are also substrates and inhibitors of P-gp. Due to competitive inhibition of the P-gp transport system, coadministration may lead to increased intestinal absorption and/or decreased hepatic excretion of either product. The resulting increased drug bioavailability could lead to increased adverse events, including serious myopathies in the case of higher than normal statin plasma concentrations. For example, P-gp inhibition was suspected in a case report involving a patient presenting to the emergency room with rhabdomyolysis, causing third-degree AV block. The patient's medication history included atorvastatin (> 1 year history), esomeprazole (6-week history), and clarithromycin (500 mg x 3 doses prior to admission). Symptoms of weakness, shortness of breath, and chest pain coincided with the start of esomeprazole therapy. Due to the timing of symptom onset, clinicians suspected that esomeprazole likely increased atorvastatin plasma concentrations leading to rhabdomyolysis and further complications. Although competitive inhibition of CYP isoenzyme metabolism could have played a minor role in the interaction, the main pathway was thought to be competitive P-gp inhibition. Caution is therefore warranted when combining atorvastatin, lovastatin, red yeast rice (structurally similar to lovastatin), or simvastatin with esomeprazole, lansoprazole, omeprazole, or pantoprazole. Substituting with dexlansoprazole or rabeprazole may represent a safer alternative. Treatment with pravastatin, fluvastatin, and rosuvastatin may also decrease the risk of a P-gp interaction.
    Sofosbuvir; Velpatasvir: Coadministration of proton pump inhibitors (PPIs) with velpatasvir is not recommended. If it is considered medically necessary to coadminister, velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Other PPIs have not been studied; however, it may be prudent to separate the administration of the other PPIs similarly. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
    Solifenacin: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Sorafenib: Sorafenib displays pH-dependent aqueous solubility; therefore, concomitant use of sorafenib and agents that increase the gastric pH, such as proton pump inhibitors (PPIs), may result in decreased plasma exposure of sorafenib. However, there was no clinically significant change in sorafenib exposure following a single oral dose of sorafenib administered after 5 days of omeprazole 40 mg/day. No sorafenib dosage adjustment is necessary.
    St. John's Wort, Hypericum perforatum: Coadministration of St. John's Wort, Hypericum perforatum (300 mg three times daily) for 14 days with a one time dose of omeprazole (20 mg) on day 15 resulted in decreased omeprazole plasma concentrations in healthy subjects. Omeprazole AUC was reduced by approximately 40% in both poor and extensive metabolizers of CYP2C19. The clinical significance of this interaction is not clear; however, due to variations in the amounts of active ingredient in herbal products, the magnitude of this interaction and the resultant clinical effect may vary. St. John's Wort induces both CYP3A4 and CYP2C19 dependent metabolism of omeprazole. Since, proton pump inhibitors (PPIs) are primary substrates of the CYP2C19 enzyme, patients taking St. John's Wort concomitantly with a PPI should be monitored for PPI efficacy.
    Sucralfate: Sucralfate has been shown to delay absorption and reduce the bioavailability of lansoprazole by about 17%. Lansoprazole should be taken no less than 30 minutes before sucralfate if these drugs are to be used concomitantly.
    Tacrolimus: Tacrolimus is metabolized via the hepatic cytochrome P-450 (CYP) 3A4. Lansoprazole may potentially inhibit CYP3A4-mediated metabolism of tacrolimus and thereby substantially increase tacrolimus whole blood concentrations. In addition to being a CYP3A4 substrate, lansoprazole is also a CYP2C19 substrate. Patients who are intermediate or poor CYP2C19 metabolizers as compared to those patients who are efficient CYP2C19 metabolizers may have more dramatic increases in their tacrolimus whole blood concentrations. Increased whole blood concentrations of tacrolimus may lead to nephrotoxicity or other side effects.
    Tamoxifen: In vitro, lansoprazole is a weak CYP2C9 and CYP2C19 inhibitor. Tamoxifen is metabolized by CYP3A4, CYP2D6, and to a lesser extent by both CYP2C9 and CYP2C19, to other potent, active metabolites including endoxifen, which have up to 33 times more affinity for the estrogen receptor than tamoxifen. These metabolites are then inactivated by sulfotransferase 1A1 (SULT1A1). Additionally, lansoprazole is a CYP3A4 and P-glycoprotein (P-gp) substrate; tamoxifen inhibits both CYP3A4 and P-gp. Theoretically, concomitant use may result in increased lansoprazole side effects and decreased concentrations of the active metabolites of tamoxifen which can compromise efficacy; the clinical significance of this interaction is not known.
    Telaprevir: Close clinical monitoring is advised when administering lansoprazole with telaprevir due to an increased potential for lansoprazole-related adverse events. If lansoprazole dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of lansoprazole. Lansoprazole is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated lansoprazole plasma concentrations.
    Telithromycin: Concentrations of lansoprazole may be increased with concomitant use of telithromycin. Lansoprazole is a CYP3A4 and P-glycoprotein (PGP) substrate and telithromycin is a strong CYP3A4 inhibitor and potential PGP inhibitor. Patients should be monitored for increased side effects.
    Temsirolimus: Use caution if coadministration of temsirolimus with lansoprazole is necessary, and monitor for an increase in temsirolimus- and lansoprazole-related adverse reactions. Temsirolimus is a P-glycoprotein (P-gp) substrate/inhibitor in vitro, while lansoprazole is also a P-gp substrate/inhibitor. Pharmacokinetic data are not available for concomitant use of temsirolimus with P-gp inhibitors or substrates, but exposure to both lansoprazole and temsirolimus (and active metabolite, sirolimus) is likely to increase.
    Tenofovir, PMPA: Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as lansoprazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Terbinafine: Due to the risk for terbinafine related adverse effects, caution is advised when coadministering lansoprazole. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9 and CYP2C19; lansoprazole is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Theophylline, Aminophylline: Concomitant use of theophylline, a CYP1A2 and CYP3A substrate, and lansoprazole has led to a small increase in theophylline clearance. Aminophylline may require dosage adjustment when therapy with lansoprazole is initiated or discontinued. Concomitant use of theophylline, a CYP1A2 and CYP3A substrate, and lansoprazole has led to a small increase in theophylline clearance. Theophylline may require dosage adjustment when therapy with lansoprazole is initiated or discontinued.
    Thiazide diuretics: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Thiopental: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Barbiturates induce hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs (e.g., CYP3A4, CYP2C19). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If barbiturates and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Ticagrelor: Coadministration of ticagrelor and lansoprazole may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and lansoprazole is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding.
    Tigecycline: Coadministration of P-glycoprotein (P-gp) inhibitors, such as lansoprazole, may increase tigecycline serum concentrations. Based on an in vitro study, tigecycline is a P-gp substrate; however, the potential contribution of P-gp-mediated transport to the in vivo disposition of tigecycline is not known.
    Tipranavir: Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Tipranavir markedly induces the hepatic cytochrome P-450 enzyme CYP2C19, an enzyme responsible for the metabolism of PPIs. However, since tipranavir is not given unless it is co-prescribed with ritonavir, a known marked enzyme inhibitor, a reduction in PPI metabolism may be unlikely to occur. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If tipranavir and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Tolterodine: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Topotecan: Avoid the concomitant use of lansoprazole, a P-glycoprotein (P-gp) inhibitor, with oral topotecan, a P-gp substrate; P-gp inhibitors have less of an effect on intravenous topotecan and these may be coadministered with caution. The pharmacokinetics of topotecan are unchanged when coadministered with ranitidine, which is a possible alternative to acid suppression therapy if needed. If coadministration of lansoprazole and oral topotecan is necessary, carefully monitor for increased toxicity of topotecan, including severe myelosuppression and diarrhea; this also applies to combination products containing lansoprazole, including lansoprazole; naproxen and amoxicillin; clarithromycin; lansoprazole. In a pharmacokinetic cohort study, coadministration of oral topotecan with a potent P-gp inhibitor (n = 8) increased the Cmax and AUC of topotecan by 2 to 3 fold (p = 0.008); coadministration with intravenous topotecan (n = 8) increased total topotecan exposure by 1.2-fold (p = 0.02) and topotecan lactone by 1.1-fold (not significant).
    Torsemide: Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Trihexyphenidyl: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Trospium: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Ulipristal: In vitro data indicate that ulipristal may be an inhibitor of P-glycoprotein (P-gp) at clinically relevant concentrations. Thus, co-administration of ulipristal and P-gp substrates such as lansoprazole may increase lansoprazole concentrations. With single doses of ulipristal for emergency contraception it is not clear this interaction will have clinical consequence. In the absence of clinical data, co-administration of ulipristal (when given daily) and P-gp substrates is not recommended.
    Vandetanib: Use caution if coadministration of vandetanib with lansoprazole is necessary, due to a possible increase in lansoprazole-related adverse reactions. Lansoprazole is partially a substrate of P-glycoprotein (P-gp). Coadministration with vandetanib increased the Cmax and AUC of digoxin, another P-gp substrate, by 29% and 23%, respectively.
    Vemurafenib: Consider an alternative to lansoprazole in patients who are receiving vemurafenib. Coadministration could lead to increased vemurafenib concentrations and, thus, adverse reactions and toxicities. Altered lansoprazole concentrations could also occur. Vemurafenib is a P-glycoprotein (P-gp) substrate/inhibitor and is a CYP3A4 inducer. Lansoprazole is a CYP3A4 substrate and a P-gp substrate/inhibitor.
    Venetoclax: Avoid the concomitant use of venetoclax and lansoprazole. Venetoclax is a substrate of P-glycoprotein (P-gp) and may be a P-gp inhibitor at therapeutic dose levels in the gut; lansoprazole is a substrate and an inhibitor of P-gp. Consider alternative agents. If concomitant use of these drugs is required, reduce the venetoclax dosage by at least 50% (maximum dose of 200 mg/day) and consider administering lansoprazole at least 6 hours before venetoclax. If lansoprazole is discontinued, wait 2 to 3 days and then resume the recommended venetoclax dosage (or prior dosage if less). Monitor patients for signs and symptoms of venetoclax toxicity such as hematologic toxicity, GI toxicity, and tumor lysis syndrome. In a drug interaction study (n = 11), the venetoclax Cmax and AUC values were increased by 106% and 78%, respectively, when a P-gp inhibitor was co-administered in healthy subjects.
    Vincristine Liposomal: Lansoprazole inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
    Vincristine: Lansoprazole inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
    Vinorelbine: Use caution with concurrent use of lansoprazole, a P-glycoprotein (P-gp) inhibitor, and vinorelbine, a P-gp substrate, as the metabolism of vinorelbine may be decreased; this may also apply to combination products containing lansoprazole, including amoxicillin; clarithromycin; lansoprazole and lansoprazole; naproxen. Monitor patients for an earlier onset and/or an increased severity of adverse effects including neurotoxicity and myelosuppression.
    Voriconazole: Voriconazole is an inhibitor of the CYP3A and CYP2C19 isozymes and may theoretically reduce the metabolism of substrates of these enzymes, including lansoprazole.
    Warfarin: Omeprazole (CYP2C19 inhibitor) can prolong the elimination of warfarin, particularly R-warfarin which is partially metabolized by CYP2C19. The combined use of omeprazole and warfarin has been associated with reports of increased INR and prothrombin time (PT). In addition, post-marketing reports of the combination of esomeprazole and warfarin have indicated elevations in PT. There have been reports of increased International Normalized Ratio (INR) and prothrombin time in patients receiving other proton pump inhibitors (PPIs) (including esomeprazole, lansoprazole, rabeprazole, and pantoprazole and warfarin concomitantly. It is prudent to monitor the INR more closely if these agents are combined with warfarin.
    Zonisamide: Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and lansoprazole is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.

    PREGNANCY AND LACTATION

    Pregnancy

    Lansoprazole is classified in FDA pregnancy risk category B. There are no adequate or well-controlled studies in pregnant women. Animal reproductive studies at doses up to 40 times the recommended human dose based on body surface area, revealed no evidence of impaired fertility or fetal harm. It is not known if lansoprazole crosses the human placenta; its low molecular weight (359) suggests that it has the potential to do so. Cases of inadvertent exposure and therapeutic use of lansoprazole in early gestation in humans suggest a low risk to the fetus. Nevertheless, human pregnancy data are limited and avoidance of lansoprazole as with all PPIs, especially during the first trimester, is the safest course. Lansoprazole should be used during pregnancy only when the severity of the patient's condition clearly indicates a necessity for its use. In 2009, a population-based observational cohort study explored a possible link between gastric acid suppressive therapy (e.g., proton pump inhibitors) during pregnancy and a diagnosis of allergic disease or a prescription for asthma or allergy medications in the exposed child. Among the cohort (n = 585,716), 1% of children exposed to gastric acid suppressive drugs in pregnancy received a diagnosis of allergic diease. For developing allergy or asthma, an increased OR of 1.43 and 1.51, respectively, were observed regardless of drug used, time of exposure during pregnancy, and maternal history of disease. Proposed possible mechanisms for a link include: (1) exposure to increased amounts of allergens could cause sensitization to digestion-labile antigens in the fetus; (2) the maternal Th2 cytokine pattern could promote an allergy prone phenotype in the fetus; (3) maternal allergen specific immunoglobulin could cross the placenta and sensitize fetal immune cells to food and airborne allergens. Study limitations were present and confirmation of results are necessary before further conclusions can be drawn from this data. Risk versus benefit should be considered prior to use.

    Animal studies indicate that lansoprazole is excreted into breast milk. No studies have been done to determine if lansoprazole is similarly excreted into human milk. Because of the potential for suppression of gastric acid secretion or other effects in the nursing infant, lansoprazole use should be avoided during breast-feeding. A decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother's condition. Alternative therapies for consideration include antacids and H2 blockers.

    MECHANISM OF ACTION

    Mechanism of Action: Lansoprazole belongs to the class of GI antisecretory agents, the substituted benzimidazoles, that suppress gastric acid secretion by inhibiting the H+/K+ ATPase enzyme system of parietal cells. An acidic environment in the parietal cell is required for conversion of gastric-acid pump inhibitors, such as lansoprazole, to the active sulfenamide metabolite. The active metabolite then inhibits the ATPase enzyme required for gastric-acid pump activation, thereby blocking the final step of acid output from the parietal cells. A significant increase in gastric pH and decrease in basal acid output follow oral administration of lansoprazole. In hypersecretory conditions, lansoprazole has a marked effect on gastric acid secretion, both basal- and pentagastrin-stimulated. Lansoprazole exerts an inhibitory effect on gastric acid for at least 24 hours, which allows a once-daily dosing schedule. Lansoprazole does not antagonize H2 or cholinergic receptors.
     
    Significant in vitro activity against Helicobacter pylori (H. Pylori) has been demonstrated for lansoprazole. Minimum inhibitory concentrations (MICs) for lansoprazole are lower than that for omeprazole. The clinical significance of this finding has not been established. Lansoprazole monotherapy increases the clearance rate of H. pylori; however, eradication does not occur without antimicrobial therapy.
     
    Serum gastrin levels increase 50—100% from baseline in the fasting state, and these increases are greater during lansoprazole therapy than during ranitidine therapy. Increases reach a plateau within 2 months and return to pretreatment levels within 4 weeks of discontinuation of lansoprazole therapy. Although prolonged hypergastrinemia has been associated with gastric tumors, a long-term study of lansoprazole for the treatment of Zollinger-Ellison syndrome did not reveal evidence to suggest that lansoprazole was implicated in tumor progression noted in two (10% of) patients. Both patients already had extensive metastatic disease.
     
    Short-term (i.e., 8-week) studies showed that lansoprazole had no effect on the endocrine system. Like omeprazole, however, lansoprazole also inhibits the hepatic cytochrome P450 oxidase system (see Drug Interactions).

    PHARMACOKINETICS

    Lansoprazole is administered orally and intervenously. Lansoprazole is about 97% bound to plasma protein. Lansoprazole is excreted into animal breast milk and possibly into human breast milk. Lansoprazole is believed to be transformed into two active inhibitors of acid secretion in the gastric parietal cells.
     
    Hepatic metabolism of lansoprazole is extensive. The two identified hepatic metabolites of lansoprazole have little antisecretory activity. Plasma elimination half-life, which is less than 2 hours, is not related to gastric antisecretory effect, which lasts more than 24 hours. Elimination is believed to occur via biliary excretion. Almost no unchanged lansoprazole is detected in urine after single-dose administration. After administration of a single dose of radio-labeled lansoprazole, one-third of the administered radiation was excreted in urine and two-thirds in the feces.
     
    Affected cytochrome P450 isoenzymes and drug transporters:
    Lansoprazole is a substrate of the cytochrome P-450 system via the CYP2C19 and CYP3A4 isoenzymes. In vitro data only suggests that lansoprazole may inhibit the CYP2C9 and CYP2C19 isoenzymes. Lansoprazole is a substrate and inhibitor of the P-glycoprotein (P-pg) transport system.

    Oral Route

    Lansoprazole should be taken in the morning at least 30 minutes before a meal on a once-daily schedule, unless large doses must be divided for hypersecretory conditions. All lansoprazole dosage forms (capsules, oral suspension, and disintegrating tablets) contain delayed-release, enteric-coated granules that release drug after they leave the stomach. Absorption of lansoprazole is rapid; mean peak plasma levels occur after about 1.7 hours. The absolute bioavailability is over 80%, which can be reduced by 50% if lansoprazole is given 30 minutes after food.

    Intravenous Route

    Following the administration of 30 mg of lansoprazole by intravenous infusion over 30 minutes to healthy subjects, plasma concentrations of lansoprazole declined exponentially with a mean terminal elimination half-life of 1.3 hours. The mean Cmax was 1705 ng/mL and the mean AUC was 3192ng•h/mL.