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Drug overview for PROTONIX IV (pantoprazole sodium):
Generic name: PANTOPRAZOLE SODIUM (pan-TOE-pra-zole)
Drug class: Peptic Ulcer Agents
Therapeutic class: Gastrointestinal Therapy Agents
Pantoprazole sodium, commonly referred to as an acid- or proton-pump inhibitor, is a gastric antisecretory agent that can suppress gastric Helicobacter pylori in patients with duodenal ulcer and/or reflux esophagitis infected with the organism.
No enhanced Uses information available for this drug.
Generic name: PANTOPRAZOLE SODIUM (pan-TOE-pra-zole)
Drug class: Peptic Ulcer Agents
Therapeutic class: Gastrointestinal Therapy Agents
Pantoprazole sodium, commonly referred to as an acid- or proton-pump inhibitor, is a gastric antisecretory agent that can suppress gastric Helicobacter pylori in patients with duodenal ulcer and/or reflux esophagitis infected with the organism.
No enhanced Uses information available for this drug.
DRUG IMAGES
PROTONIX IV 40 MG VIAL
The following indications for PROTONIX IV (pantoprazole sodium) have been approved by the FDA:
Indications:
Erosive esophagitis
Gastric hypersecretion with systemic mastocytosis
Gastroesophageal reflux disease
Pathological gastric acid hypersecretory condition
Zollinger-Ellison syndrome
Professional Synonyms:
Adenomatosis partial multiple endocrine
Gastric acid hypersecretory conditions due to disease
Gastro-esophageal reflux
GE reflux disease
Pancreatic ulcerogenic tumor syndrome
Pathological gastric acid hypersecretory states
Pathological hypersecretion state
Pathological hypersecretory condition
Systemic mast cell disease with gastric hypersecretion
Z-E syndrome
Indications:
Erosive esophagitis
Gastric hypersecretion with systemic mastocytosis
Gastroesophageal reflux disease
Pathological gastric acid hypersecretory condition
Zollinger-Ellison syndrome
Professional Synonyms:
Adenomatosis partial multiple endocrine
Gastric acid hypersecretory conditions due to disease
Gastro-esophageal reflux
GE reflux disease
Pancreatic ulcerogenic tumor syndrome
Pathological gastric acid hypersecretory states
Pathological hypersecretion state
Pathological hypersecretory condition
Systemic mast cell disease with gastric hypersecretion
Z-E syndrome
The following dosing information is available for PROTONIX IV (pantoprazole sodium):
Dosage of pantoprazole sodium is expressed in terms of pantoprazole.
No enhanced Administration information available for this drug.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| PROTONIX IV 40 MG VIAL | Maintenance | Adults infuse 40 mg by intravenous route once daily |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| PANTOPRAZOLE SODIUM 40 MG VIAL | Maintenance | Adults infuse 40 mg by intravenous route once daily |
The following drug interaction information is available for PROTONIX IV (pantoprazole sodium):
There are 2 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Atazanavir; Nelfinavir/Proton Pump Inhibitors SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Proton pump inhibitors increase gastric pH. As gastric pH increases, the solubility of atazanavir and nelfinavir decreases.(1,2) Omeprazole has been shown to inhibit nelfinavir metabolism by CYP2C19.(3) CLINICAL EFFECTS: Concurrent use of atazanavir(1-2,4-8) or nelfinavir(3,8-9) and a proton pump inhibitor may result in decreased levels and effectiveness of atazanavir or nelfinavir. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US and Australian manufacturer of atazanavir states that treatment naive patients requiring a proton pump inhibitor should receive 300 mg atazanavir with 100 mg ritonavir. The proton pump inhibitor should not exceed a dose comparable to omeprazole 20 mg daily and should be administered 12 hours before atazanavir/ritonavir.(1,2) Atazanavir should not be administered with proton pump inhibitors without concurrent ritonavir in adults or pediatric patients of at least 13 years of age and weighing at least 40 kg.(1,2) The US and Australian manufacturer of atazanavir states that proton pump inhibitors should not be administered with atazanavir in treatment experienced patients.(1,2) Data are insufficient to recommend a dose of atazanavir in patients weighing less than 40 kg and receiving a proton pump inhibitor.(1) The Canadian and UK manufacturer of atazanavir states that the coadministration of atazanavir and proton pump inhibitors is not recommended. If coadministration is necessary, the dose of atazanavir should be increased to 400 mg daily taken with ritonavir 100 mg daily, and the dose of the proton pump inhibitor should not exceed the equivalent of omeprazole 20 mg.(10,11) The UK manufacturer of esomeprazole states that concurrent use with atazanavir is contraindicated.(9) The US manufacturer of esomeprazole(4) and omeprazole(5) states that concurrent use of atazanavir or nelfinavir is not recommended. The US manufacturers of dexlansoprazole (6), lansoprazole,(7) and pantoprazole(8) state that atazanavir and nelfinavir should not be coadministered with proton pump inhibitors. DISCUSSION: In a study of 16 subjects, atazanavir (400 mg daily) area-under-curve (AUC), maximum concentration (Cmax) and minimum concentration (Cmin) decreased 94%, 96% and 95% respectively, when given with omeprazole (40 mg daily). Omeprazole AUC and Cmax increased 145% and 124% respectively.(1) In a study of 15 subjects, atazanavir AUC, Cmax and Cmin decreased 76%, 72% and 78% respectively, when given with omeprazole (40 mg daily) and ritonavir (100 mg daily).(1) In a study in 13 subjects, administration of omeprazole (20 mg daily) 12 hours before atazanavir/ritonavir (300/100 mg daily) decreased atazanavir Cmax, AUC, and Cmin by 39%, 42%, and 46%, respectively; however, the atazanavir AUC and Cmin were 10% and 2.4-fold higher than average levels seen with atazanavir 400 mg alone.(1) In a study in 14 subjects, administration of omeprazole (20 mg daily) 1 hour before atazanavir/ritonavir (400/100 mg daily) decreased atazanavir Cmax, AUC, and Cmin by 31%, 30%, and 31%, respectively; however, the atazanavir AUC and Cmin were 32% and 3.3-fold higher than average levels seen with atazanavir 400 mg alone.(1) In a study in 10 healthy subjects, concurrent administration of lansoprazole (60 mg daily for 2 days) with atazanavir (400 mg) decreased atazanavir AUC by 94%.(14) In a case report, concurrent esomeprazole decreased atazanavir, but not fosamprenavir levels in a 65 year-old HIV-positive male.(15) In a study in 16 healthy, HIV-negative subjects, the concurrent administration of omeprazole or ranitidine with ritonavir-boosted darunavir had no effect on darunavir pharmacokinetics.(16) In a study in healthy subjects, the concurrent administration of esomeprazole (20 mg daily) with either fosamprenavir (1400 mg twice daily) or fosamprenavir (700 mg twice daily) and ritonavir (100 mg twice daily) for 14 days had no effect on amprenavir pharmacokinetics.(17) In a study in 19 subjects, concurrent omeprazole (40 mg daily) and nelfinavir (1250 mg twice daily) for 4 days decreased nelfinavir AUC, Cmax, and Cmin by 36%, 37%, and 39%.(7,17) The AUC, Cmax, and Cmin of the active M8 metabolite of nelfinavir decreased by 92%, 89%, and 75%, respectively.(4,17) A retrospective review of nelfinavir levels found concurrent use of omeprazole decreased the median M8/nelfinavir ratio.(12) In a case report a 56 year old HIV infected male received omeprazole (40mg daily) and atazanavir/ritonavir (300/100mg) for ten months. Investigators used Bayesian models to determine atazanavir exposure, and found atazanavir levels to be in the 25th percentile of boosted levels, but still above the 75th percentile for unboosted atazanavir.(20) A retrospective review of 76 patients taking proton pump inhibitors and 66 patients not using proton pump inhibitors found no association with a higher virologic failure rate in patients receiving proton pump inhibitors.(21) In a case report, a 50 year-old HIV-infected male with a CD4 count of 1095 cells/ml and an HIV load of 88 copies/ml on a nelfinavir based regimen was switched to an atazanavir/ritonavir (300/100mg daily) regimen. The patient was taking omeprazole (20mg daily) and admitted to taking the atazanavir at 150mg twice daily. The patients CD4 count dropped to 830 cells/ml, but his HIV load dropped to <75 copies/ml. The investigators summarized concurrent use of omeprazole did not adversely affect this patient's virologic load.(22) In a study in 18 healthy subjects, concurrent omeprazole (40 mg daily) with saquinavir/ritonavir (1000/100 mg twice daily) for 4 days increased saquinavir AUC by 83%. No toxicities were noted.(18) In a study in 12 healthy subjects, concurrent omeprazole (40 mg daily) with saquinavir/ritonavir (1000/100 mg twice daily) for 7 weeks increased saquinavir AUC, Cmin, and Cmax by 54%, 73%, 55% respectively. Omeprazole 2 hours prior to saquinavir/ritonavir increased saquinavir AUC, Cmin, and Cmax by 67%, 97%, and 65% respectively. No toxicities were noted.(23) In a study of 14 healthy subjects, concurrent omeprazole (20 mg daily and 40 mg daily) with indinavir (800mg daily) for 7 days decreased indinavir AUC by 34% and 47% respectively and no statistical changes were seen in the Cmax or Tmax of indinavir. When omeprazole (40mg daily) was given with indinavir/ritonavir (800mg/200mg daily) for 7 days indinavir AUC increased by 55% and no statistical changes were seen in indinavir Cmax or Tmax. Omeprazole (40mg daily) showed a Cmax increase of 50% and a half-life increase of 100% in the presence of ritonavir.(24) In a study of 19 healthy subjects, concurrent omeprazole (20 mg daily) with fosamprenavir/ritonavir (1400/200 mg daily) or atazanavir/ritonavir (300/100)for 3 weeks showed no effect on amprenavir pharmacokinetics, but decreased atazanavir AUC and Cmin by 27%.(25) In a retrospective review of 15 HIV-infected patients receiving indinavir (800mg three times daily), nine patients were also receiving omeprazole (20-40mg daily). Of these nine patients, four had plasma concentrations of indinavir below the 95% confidence interval of plasmas concentration in patients receiving indinavir alone, four were within the 95% confidence interval, and one was above the 95% confidence interval.(26) In a case report, a 40 year-old HIV-infected male with extensive antiretroviral history and virological failure began atazanavir/ritonavir (300/100mg daily). The patient was restarted on lansoprazole during atazanavir/ritonavir therapy, and despite lansoprazole and tenofovir therapy the patients plasma concentrations of atazanavir remained consistent with historical values, and the patients Cmin stayed well above the established values for the combination of atazanavir/ritonavir with tenofovir.(27) In a study of 68 healthy subjects, coadministration of omeprazole (40mg daily) with lopinavir/ritonavir (400/100mg twice daily or 800/200mg once daily) showed no statistical change in pharmacokinetics.(28,29) However, when given with atazanavir/ritonavir (300/100 daily) bioavailability of atazanavir decreased by 48-62%.(28) One or more of the drug pairs linked to this monograph have been included in a list of interactions that should be considered "high-priority" for inclusion and should not be inactivated in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology. |
ATAZANAVIR SULFATE, EVOTAZ, REYATAZ, VIRACEPT |
| Rilpivirine/Proton Pump Inhibitors SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Rilpivirine requires an acidic medium for absorption. The proton pump inhibitor induced decrease in gastric pH may result in a decrease in rilpivirine absorption.(1) CLINICAL EFFECTS: Concurrent use of a proton pump inhibitor may result in decreased levels and effectiveness of rilpivirine, as well as the development of resistance.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of rilpivirine states that concurrent use of proton pump inhibitors is contraindicated.(1) When substituting antacids for proton pump inhibitors in patients maintained on rilpivirine, administer the antacid at least 2 hours before or 4 hours after rilpivirine.(1) When substituting H2 antagonists for proton pump inhibitors in patients maintained on rilpivirine, administer the H2 antagonist at least 12 hours before or 4 hours after rilpivirine.(1) DISCUSSION: In a study in 16 subjects, omeprazole (20 mg daily) decreased the maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) of rilpivirine (150 mg daily) by 40%, 40%, and 33%, respectively. The Cmax and AUC of omeprazole decreased by 14% and 14%, respectively.(1) In a study in 24 subjects, famotidine (40 mg single dose) administered 12 hours before a single dose of rilpivirine (150 mg) had no significant effect on rilpivirine Cmax or AUC.(1) In a study in 23 subjects, famotidine (40 mg single dose) administered 2 hours before a single dose of rilpivirine (150 mg) decreased the rilpivirine Cmax and AUC by 85% and 76%, respectively.(1) In a study in 24 subjects, famotidine (40 mg single dose) administered 4 hours after a single dose of rilpivirine (150 mg) increased the rilpivirine Cmax and AUC by 21% and 13%, respectively.(1) |
COMPLERA, EDURANT, JULUCA, ODEFSEY |
There are 15 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Selected Kinase Inhibitors/Proton Pump Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The solubility of bosutinib,(1) dacomitinib,(2) dasatinib,(3) erlotinib,(4) gefitinib,(5) neratinib,(6) nilotinib,(7) pazopanib(8), and pexidartinib (9) is pH dependent. Changes in gastric pH from proton pump inhibitors may decrease the absorption of bosutinib,(1) dacomitinib,(2) dasatinib,(3) erlotinib,(4) gefitinib,(5) neratinib,(6) nilotinib,(7) pazopanib,(8) and pexidartinib.(9) CLINICAL EFFECTS: Use of proton pump inhibitors may result in decreased levels and effectiveness of bosutinib,(1) dacomitinib,(2) dasatinib,(3) erlotinib,(4) gefitinib,(5) neratinib,(6) nilotinib,(7) pazopanib,(8) and pexidartinib.(9) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the use of proton pump inhibitors (PPIs) in patients receiving treatment with bosutinib,(1) dacomitinib,(2) dasatinib,(3) erlotinib,(4) gefitinib,(5) neratinib,(6) nilotinib,(7) pazopanib,(8) and pexidartinib.(9) Consider the use of short-acting antacids in these patients.(1-9) If antacids are used, separate the administration times by several hours(1-9) but at least 2 hours for bosutinib,(1) dasatinib,(3) nilotinib,(7) and pexidartinib(9), 6 hours for gefitinib,(5) and 3 hours for neratinib.(6) If PPIs are required with gefitinib, administer gefitinib 12 hours after the last dose or 12 hours before the next dose of the PPI. Administer gefitinib 6 hours before or after H2-antagonists or antacids.(5) If H2 antagonist therapy is used with bosutinib, separate administration by at least 2 hours.(1) If H2 antagonist therapy is required with dacomitinib, dacomitinib must be given once daily 10 hours after the H2 blocker and 6 hours before the next dose of the H2 blocker.(2) If H2 antagonist therapy is required with erlotinib, neratinib, nilotinib, or pexidartinib, the kinase inhibitor must be given 10 hours after the H2 blocker and at least 2 hours before the next dose of the H2 blocker.(4,6,7,9) If H2 antagonist therapy is required with gefitinib, gefitinib should be given at least 6 hours before or after the H2 antagonist.(5) The manufacturer of Phyrago states that it can be administered with gastric acid reducing agents. Administration times should be separated with antacids. DISCUSSION: In a study, concurrent rabeprazole decreased the Cmax and AUC of dacomitinib by 51% and 39%, respectively.(2) In a study in 24 healthy subjects, administration of a single dose of dasatinib (50 mg) 10 hours after famotidine decreased dasatinib area-under-curve (AUC) and maximum concentration (Cmax) by 61% and 63%, respectively.(3) In a study in 14 healthy subjects, administration of a single dose of dasatinib (100 mg) 22 hours after omeprazole (40 mg at steady state) decreased dasatinib AUC and Cmax by 43% and 42%, respectively.(3) In a study in 24 healthy subjects, simultaneous administration of dasatinib (50 mg) with aluminum hydroxide/magnesium hydroxide (30 ml) decreased dasatinib AUC and Cmax by 55% and 58%, respectively. In the same subjects, administration of the antacid 2 hours before dasatinib decreased dasatinib Cmax by 26%, but had no effect on dasatinib AUC.(3) In a study, concurrent omeprazole decreased the AUC and Cmax of erlotinib by 46% and 61%, respectively.(4) In a study, administration of erlotinib two hours after a dose of ranitidine (300 mg), erlotinib AUC and Cmax decreased by 33% and 54%, respectively. Administration of erlotinib 10 hours after and two hours before ranitidine (150 mg twice daily), erlotinib AUC and Cmax decreased by 15% and 17%, respectively.(4) In a case report, a patient that was given erlotinib (150 mg daily,) with algeldrate/magnesium hydroxide (800/400 mg four times daily 4 hours before or 2 hours after erlotinib) did not see a significant reduction in serum trough concentrations of erlotinib. When the patient was switched to intravenous pantoprazole via continuous infusion (8 mg per hour), serum erlotinib levels decreased significantly below minimal trough concentrations for effective tyrosine kinase inhibition. When the patient was switched to oral pantoprazole (40 mg twice daily), serum trough levels of erlotinib returned to therapeutic levels.(9) In a study in healthy subjects, high dose ranitidine with sodium carbonate was administered to maintain gastric pH above 5.0 and gefitinib AUC decreased 47%.(5) In a study in 15 healthy subjects, lansoprazole (30 mg at steady state) decreased the Cmax and AUC of a single dose of neratinib (240 mg) by 71% and 65%, respectively.(6) In a study in 22 healthy subjects, pretreatment with esomeprazole (40 mg daily), decreased the Cmax and AUC of a single dose of nilotinib (400 mg) by 27% and 34%, respectively.(7,10) Increasing the dosage of nilotinib or separating the administration time of nilotinib and the proton pump inhibitor is not expected to eliminate the interaction.(7) There were no significant changes in nilotinib pharmacokinetics when famotidine was administered 10 hours before or 2 hours after nilotinib.(7) There were no significant changes in nilotinib pharmacokinetics when an antacid (aluminum hydroxide/magnesium hydroxide/simethicone) was administered 2 hours before or after nilotinib.(7) In a study in 13 patients, esomeprazole (40 mg daily for 5 days) decreased the Cmax and AUC of pazopanib (400 mg daily) by 42% and 40%, respectively, when compared to the administration of pazopanib alone.(11) In an open-label, crossover study in 17 evaluable patients, omeprazole (40 mg daily) had no significant effects on the pharmacokinetics, pharmacodynamics, or safety of bortezomib (1.3 mg/m2).(12) Coadministration of esomeprazole decreased pexidartinib Cmax and AUC by 55% and 50%. (13) Phyrago is not sensitive to increased gastric pH due to its polymer formulation. No clinically significant dasatinib pharmacokinetic changes were seen with concurrent administration of Phyrago with omeprazole (proton pump inhibitor) or famotidine (H2 receptor antagonist).(14) |
BOSULIF, DANZITEN, DASATINIB, ERLOTINIB HCL, GEFITINIB, IRESSA, NERLYNX, NILOTINIB HCL, PAZOPANIB HCL, SPRYCEL, TARCEVA, TASIGNA, TURALIO, VIZIMPRO, VOTRIENT |
| Posaconazole Suspension/H2 Antagonists; Proton Pump Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: H2 antagonists and proton pump inhibitors (PPIs) increase the stomach pH, possibly reducing gastrointestinal absorption of posaconazole suspension. CLINICAL EFFECTS: Concurrent use of H2 antagonists or proton pump inhibitors (PPIs) may result in decreased effectiveness of posaconazole suspension. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the concurrent use of posaconazole suspension with H2 antagonists or proton pump inhibitors (PPIs).(1) If H2 antagonists or PPI therapy is required, use the tablet formulation or powder mix formulation of posaconazole. DISCUSSION: Concurrent cimetidine (400 mg twice daily) decreased both posaconazole (200 mg daily) maximum concentration (Cmax) and area-under-curve (AUC) levels by 39%.(1) No significant effects with other H2 blockers have been noted.(1) Esomeprazole (40 mg daily for 3 days) decreased the Cmax and AUC of a single dose of posaconazole suspension (400 mg) by 46% and 32%, respectively.(1) In a study of posaconazole levels in patients with acute myeloid leukemia or myelodysplastic syndrome, use of pantoprazole was associated with decreased posaconazole levels.(3) In a cross-over study in 5 healthy subjects, esomeprazole decreased the Cmax and AUC of posaconazole suspension by 37% and 84%, respectively. Simultaneous intake of Coca-Cola did not completely counteract the effects of esomeprazole.(4) In a study in healthy subjects, esomeprazole decreased the Cmax and AUC of posaconazole suspension by 55% and 49%, respectively. Simultaneous intake of Coca-Cola did not completely counteract the effects of esomeprazole.(5) |
NOXAFIL, POSACONAZOLE |
| Methotrexate (Oncology-Injection )/Proton Pump Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Proton pump inhibitors may inhibit the active secretion of methotrexate from the kidney via inhibition of the hydrogen-potassium ATPase(1) and may reduce uptake of methotrexate into breast cancer resistance protein via competitive inhibition.(2,3) CLINICAL EFFECTS: The concurrent use of methotrexate and proton pump inhibitors may result in elevated levels of methotrexate and increased methotrexate-related adverse effects and toxicities, leading to increased risk of severe neurotoxicity, stomatitis, and myelosuppression, including neutropenia. PREDISPOSING FACTORS: Risk factors for methotrexate toxicity include: - High-dose oncology regimens - Impaired renal function, ascites, or pleural effusions PATIENT MANAGEMENT: For patients receiving high dose methotrexate with leucovorin rescue, consider discontinuation of proton pump inhibitors for the duration of therapy. Patients receiving concurrent use of methotrexate and proton pump inhibitors should be monitored closely for elevated methotrexate levels and methotrexate toxicity. The US manufacturer of omeprazole states that secretory ability returns gradually over three to five days following discontinuation.(4) Therefore, it would seem prudent to discontinue proton pump inhibitors several days prior to methotrexate therapy. DISCUSSION: In a clinical trial in 74 patients on high dose (1-5 G/m2) methotrexate therapy, data was examined to determine if proton pump inhibitor (omeprazole, pantoprazole, rabeprazole) use affects methotrexate elimination. Delayed elimination was found to be more frequent in those with co-administration of a proton pump inhibitor (31.7% vs. 13.8%), resulting in higher plasma methotrexate concentrations at 24, 48, and 74 hours. The effect was seen with lansoprazole, omeprazole, pantoprazole, and rabeprazole.(2) There are three case reports(1,5,6) of elevated methotrexate levels or delayed methotrexate elimination resulting from concurrent administration of high dose methotrexate and omeprazole, including one patient(6) that developed severe mucositis. In each case, omeprazole was discontinued and normal methotrexate kinetics were observed on subsequent cycles with no further adverse effects noted. In a case report of a 59 year-old male on low dose (15 mg weekly) methotrexate, administration of pantoprazole (20 mg daily) was found to increase the AUC of the metabolite 7-hydroxymethotrexate by 70%.(7) In a clinical trial, 28 adults with rheumatoid arthritis on low dose (7.5-15 mg weekly) methotrexate were assigned to receive lansoprazole (30 mg daily) and naproxen (500 mg twice daily) on Days 1-7 of therapy. The half life of the metabolite 7-hydroxymethotrexate was prolonged with concurrent administration, but no other statistically significant differences were found in regards to the plasma concentration profiles of methotrexate or 7-hydroxymethotrexate.(8) |
METHOTREXATE, METHOTREXATE SODIUM |
| Ledipasvir; Velpatasvir/Proton Pump Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The aqueous solubility of ledipasvir and velpatasvir is pH dependent. Higher gastric pH leads to lower solubility which may reduce ledipasvir and velpatasvir absorption.(1-3) CLINICAL EFFECTS: Coadministration of proton pump inhibitors (PPIs) may reduce the bioavailability of ledipasvir and velpatasvir, leading to decreased systemic levels and effectiveness.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Omeprazole 20 mg daily, or comparable doses of other PPIs, may be administered simultaneously with ledipasvir-sofosbuvir under fasting conditions.(1) Coadministration of proton pump inhibitors is not recommended with sofosbuvir-velpatasvir. When concomitant proton pump inhibitor use is necessary in patients receiving sofosbuvir-velpatasvir, velpatasvir-sofosbuvir should be administered with food and taken 4 hours before omeprazole 20 mg. Use with other proton pump inhibitors has not been studied.(2) Omeprazole 20 mg daily may be administered with sofosbuvir-velpatasvir-voxilaprevir. Use with other proton pump inhibitors has not been studied.(3) When clinically appropriate, consider use of H2 blockers or antacids.(1-3) DISCUSSION: In an interaction study, omeprazole 20 mg given once daily simultaneously with ledipasvir-sofosbuvir, decreased ledipasvir exposure (AUC) by 4%. When omeprazole 20 mg once daily was given 2 hours prior to ledipasvir-sofosbuvir dose, ledipasvir exposure (AUC) decreased approximately 50%.(1) In an interaction study, omeprazole 20 mg given once daily simultaneously with sofosbuvir-velpatasvir decreased velpatasvir exposure (AUC) by 37%. When omeprazole 20 mg once daily was given 12 hours prior to sofosbuvir-velpatasvir dose, velpatasvir exposure (AUC) decreased 57%. When omeprazole 20 mg once daily was given 2 hours prior to sofosbuvir-velpatasvir dose, velpatasvir AUC decreased 48%. When omeprazole 20 mg once daily was given 4 hours after sofosbuvir-velpatasvir dose, velpatasvir AUC decreased 33%. When omeprazole 40 mg once daily was given 4 hours after sofosbuvir-velpatasvir dose, velpatasvir AUC decreased 56%.(2) In an interaction study, when omeprazole 20 mg once daily was given 2 hours prior to the sofosbuvir-velpatasvir-voxilaprevir dose, sofosbuvir AUC, velpatasvir AUC, and voxilaprevir AUC decreased 27%, 54%, and 20%, respectively. When omeprazole 20 mg once daily was given 4 hours after the sofosbuvir-velpatasvir-voxilaprevir dose, sofosbuvir AUC, velpatasvir AUC, and voxilaprevir AUC decreased 18%, 51%, and 5%, respectively %.(3) Proton pump inhibitors linked to this monograph are: dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole. |
EPCLUSA, HARVONI, LEDIPASVIR-SOFOSBUVIR, SOFOSBUVIR-VELPATASVIR, VOSEVI |
| Capecitabine/Proton Pump Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The aqueous solubility of capecitabine is pH dependent. Higher gastric pH leads to lower solubility and altered tablet dissolution which may reduce capecitabine absorption.(1,2) CLINICAL EFFECTS: Coadministration of proton pump inhibitors (PPIs) may reduce the bioavailability of capecitabine, leading to decreased systemic levels and effectiveness.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of proton pump inhibitors with capecitabine may decrease bioavailability. When clinically appropriate, consider using H2 blockers or antacids. DISCUSSION: A retrospective study in early stage colorectal cancer patients treated with adjuvant monotherapy capecitabine examined recurrence-free survival (RFS) and overall survival (OS) in 1335 patients with and without concurrent proton pump inhibitor (PPI) therapy. The PPI group was defined as a prescription for a PPI filled at any point in time during capecitabine treatment. Patients in the capecitabine with concurrent PPI group had a statistically significant decrease in 5-year RFS (74% v 83%; hazard ratio (HR) 1.89; 95% confidence interval (CI) 1.07-3.35; p=0.03) compared to capecitabine without PPI therapy. OS was not significantly different between groups (81% PPI v 78% non-PPI; HR 1.13; 95% CI 0.6-2.14; p=0.7). After adjusting for male gender, stage III colorectal cancer, advance age >68, poorer ECOG PS, there was a trend toward decreased RFS in PPI patients (HR 1.65; 95% CI 0.93-2.94; p=0.09).(1) An ad hoc analysis of the TRIO-013/LOCiC trial examined coadministration of PPI therapy, defined as 20% or more overlap between a PPI prescription and trial treatment duration with capecitabine and/or lapatinib, on progression-free survival (PFS) and overall survival (OS). The secondary analysis examined 545 patients in which 42% were on concurrent PPI therapy. Patients in the non-PPI group had an improved median PFS (5.7 v 4.2 months; HR 1.55; 95% CI 1.29-1.81; p<0.001) and median OS (11.3 v 9.2 months; HR 1.34; 95% CI 1.06-1.62; p=0.04) compared with PPI users. A multivariate analysis reviewed effects of PPIs on both PFS and OS with capecitabine alone and found effects of PPI use on both PFS and OS was still significant (HR 1.68; p<0.001 and HR 1.41; p=0.001, respectively).(2) In a study in 12 subjects, concomitant administration of capecitabine with aluminum-magnesium hydroxide containing antacid 20 mL increased area-under-curve (AUC) and concentration maximum (Cmax) by 16% and 35%, respectively.(3) Proton pump inhibitors linked to this monograph include: dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole. |
CAPECITABINE, XELODA |
| Slt Proton Pump Inhibitors/Strong 2C19 and 3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong CYP2C19 and CYP3A4 inducers may induce the metabolism of dexlansoprazole, lansoprazole, or pantoprazole.(1-3) CLINICAL EFFECTS: Concurrent use of strong CYP2C19 and CYP3A4 inducers may decrease systemic levels and effectiveness of lansoprazole, dexlansoprazole, or pantoprazole.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturers of lansoprazole and dexlansoprazole recommend avoiding concurrent use of CYP2C19 or CYP3A4 inducers.(1,2) Although the manufacturer of pantoprazole does not mention an interaction with CYP2C19 inducers, pantoprazole is also a substrate of CYP2C19 and CYP3A4.(3) If concurrent therapy is warranted, monitor closely for loss of efficacy. Although specific dosing recommendations are not available, a higher dose of the proton pump inhibitor may be considered to maintain PPI efficacy. DISCUSSION: Decreased exposure of lansoprazole, dexlansoprazole, or pantoprazole is expected when used concomitantly with strong CYP2C19 and CYP3A4 inducers. Strong CYP2C19 and CYP3A4 inducers linked to this monograph include: apalutamide, efavirenz, enzalutamide, fosphenytoin, phenytoin, rifampin, and St. John's Wort.(4,5) |
CEREBYX, DILANTIN, DILANTIN-125, EFAVIRENZ, EFAVIRENZ-EMTRIC-TENOFOV DISOP, EFAVIRENZ-LAMIVU-TENOFOV DISOP, ERLEADA, FOSPHENYTOIN SODIUM, PHENYTEK, PHENYTOIN, PHENYTOIN SODIUM, PHENYTOIN SODIUM EXTENDED, RIFADIN, RIFAMPIN, SYMFI, SYMFI LO, XTANDI |
| Secretin/H2 Antagonists; Proton Pump Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: H2 antagonists and proton pump inhibitors (PPIs) may result in an incorrect secretin stimulation test result.(1) CLINICAL EFFECTS: Concurrent use of H2 antagonists and proton pump inhibitors (PPIs) may impact the accuracy of the secretin stimulation test.(1) PREDISPOSING FACTORS: Patients with alcoholic or other liver disease may be hyperresponsive to stimulation with a secretin stimulation test, masking the presence of coexisting pancreatic disease. Consider additional testing and clinical assessment for diagnosis.(1) PATIENT MANAGEMENT: The US manufacturer of human secretin states concurrent use of H2 antagonists and proton pump inhibitors (PPIs) at the time of stimulation testing may cause the patient to be hyperresponsive to secretin stimulation and suggest false gastrinoma results. The manufacturer recommends discontinuing H2 antagonists at least 2 days prior to testing. The US manufacturer of vonoprazan recommends stopping vonoprazan at least 4 weeks prior to testing.(2-3) Consult prescribing information for PPIs before administering prior to a secretin stimulation test.(1) DISCUSSION: Concurrent use of H2 antagonists and proton pump inhibitors (PPIs) may impact the accuracy of the secretin stimulation test.(1) |
CHIRHOSTIM |
| Selpercatinib/Proton Pump Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The solubility of selpercatinib is pH dependent. Increase in gastric pH from proton pump inhibitors (PPIs) may decrease the solubility and absorption of selpercatinib.(1) CLINICAL EFFECTS: Use of proton pump inhibitors may result in decreased levels and effectiveness of selpercatinib.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the use of proton pump inhibitors (PPIs), H2 antagonists, and locally acting antacids in patients receiving treatment with selpercatinib. If coadministration with PPIs cannot be avoided, take selpercatinib with food.(1) If the PPI is replaced with a H2 antagonist, take selpercatinib 2 hours before or 10 hours after the H2 antagonist.(1) If the PPI is replaced with an antacid, take selpercatinib 2 hours before or 2 hours after the antacid.(1) DISCUSSION: In a study, omeprazole decreased the area-under-curve (AUC) and maximum concentration (Cmax) of selpercatinib (administered fasting) by 69% and 88%, respectively. When selpercatinib was administered with food, omeprazole did not significantly affect selpercatinib levels.(1) |
RETEVMO |
| Selected Cephalosporins/Long Acting Antacids; H2s;PPIs SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Absorption of oral cefpodoxime or cefuroxime may be reduced in patients receiving concomitant treatment with acid reducing agents.(1-5) CLINICAL EFFECTS: Antibiotic efficacy against organisms with a high minimum inhibitory concentration (MIC) to cefpodoxime or cefuroxime could be decreased. PREDISPOSING FACTORS: Taking cefpodoxime or cefuroxime on an empty stomach magnifies this effect. PATIENT MANAGEMENT: If possible, avoid the use of H2 antagonists and proton pump inhibitors(PPIs) in patients taking cefpodoxime or cefuroxime. If concurrent therapy is needed with antacids, H2 antagonists, or PPIs, administer cefpodoxime or cefuroxime after eating to maximize oral absorption. Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: In a study of ten subjects, administration of cefpodoxime after single dose famotidine 40 mg decreased both maximum concentration (Cmax) and area-under-curve (AUC) by approximately 40 percent compared with administration of cefpodoxime on an empty stomach.(3) In a study of 17 subjects, administration of cefpodoxime after single dose ranitidine 150 mg decreased Cmax and AUC by approximately 40 percent compared with administration of cefpodoxime on an empty stomach.(4) In a study performed prior to the introduction of PPIs, administration of ranitidine 300 mg and sodium bicarbonate followed by cefuroxime taken on a empty stomach lowered both Cmax and AUC of cefuroxime by approximately 40 per cent compared with administration of cefuroxime alone on an empty stomach. Postprandial administration of cefuroxime in subjects taking ranitidine was similar to that of subjects taking cefuroxime on an empty stomach.(5) |
CEFPODOXIME PROXETIL, CEFUROXIME |
| Sotorasib/H2 Antagonists; Proton Pump Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The aqueous solubility of sotorasib is pH dependent. Higher gastric pH leads to lower solubility which may reduce sotorasib absorption.(1) CLINICAL EFFECTS: Coadministration of proton pump inhibitors (PPIs) or H2 antagonists may reduce the bioavailability of sotorasib, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of sotorasib with proton pump inhibitors, H2 antagonists, and antacids should be avoided. If coadministration with an acid-reducing agent is unavoidable, take sotorasib 4 hours before or 10 hours after a locally acting antacid.(1) The UK manufacturer of sotorasib states if co-administration with an acid-reducing agent (such as a PPI or an H2 antagonist) is required, sotorasib should be taken with an acidic beverage (such as cola). Alternatively, sotorasib should be taken 4 hours before or 10 hours after administration of a local antacid.(2) DISCUSSION: The solubility of sotorasib in the aqueous media decreases over the range pH 1.2 to 6.8 from 1.3 mg/mL to 0.03 mg/mL. In an interaction study, coadministration of repeat doses of omeprazole with a single dose of sotorasib decreased sotorasib maximum concentration (Cmax) by 65% and area-under-curve (AUC) by 57% under fed conditions, and decreased sotorasib Cmax by 57% and AUC by 42% under fasted conditions. Under fasted conditions, co-administration of repeat doses of omeprazole with a single dose of sotorasib and 240ml of an acidic beverage (non-diet cola) decreased sotorasib Cmax by 32% and AUC by 23%. The UK manufacturer of sotorasib states the clinical relevance of the decreased sotorasib exposure when co-administered with omeprazole and cola is unclear and sotorasib efficacy might be reduced.(2) Coadministration of a single dose of famotidine given 10 hours prior to and 2 hours after a single dose of sotorasib under fed conditions decreased sotorasib Cmax by 35% and AUC by 38%.(1) |
LUMAKRAS |
| Methylphenidate XR-ODT/H2 Antagonists;Proton Pump Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The solubility of methylphenidate extended release orally disintegrating tablets (XR-ODT) is pH-dependent. At elevated pH, methylphenidate may be released from the tablets more quickly, resulting in increased absorption.(1) CLINICAL EFFECTS: Coadministration of H2 antagonists or proton pump inhibitors (PPIs) may result in an altered pharmacokinetic profile of methylphenidate XR-ODT, which may change the effectiveness and/or adverse effects of methylphenidate XR-ODT.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of methylphenidate XR-ODT with H2 antagonists or PPIs is not recommended.(1,2) DISCUSSION: In in vitro studies, when media pH was increased from 1.2 to 6.8, percentage release of methylphenidate from the XR-ODT tablet was increased by 67% at 0.5 hours, and by 93% at 2.5 hours. The increased dissolution of methylphenidate at higher pH may result in increased drug absorption and change the concentration-time profile of methylphenidate, which is correlated with pharmacological effect.(1) |
COTEMPLA XR-ODT |
| Levoketoconazole/H2 Antagonists; Proton Pump Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The aqueous solubility of levoketoconazole is pH dependent. Higher gastric pH leads to lower solubility. H2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) increase gastric pH and may decrease the absorption of levoketoconazole.(1) CLINICAL EFFECTS: Coadministration of H2RAs or PPIs may reduce the bioavailability of levoketoconazole, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of levoketoconazole with PPIs and H2RAs should be avoided.(1) DISCUSSION: Levoketoconazole is very slightly soluble in water but soluble below pH 2. H2RAs and PPIs raise gastric pH and may impair dissolution and absorption of levoketoconazole.(1) |
RECORLEV |
| Pemetrexed/Proton Pump Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Proton pump inhibitors may inhibit the active secretion of pemetrexed from the kidney via the organic anion transporter 3 (OAT3).(1,2,3) CLINICAL EFFECTS: The concurrent use of pemetrexed and proton pump inhibitors may result in increased levels and toxicities of pemetrexed, including severe neurotoxicity, stomatitis, and myelosuppression, including neutropenia. PREDISPOSING FACTORS: Risk factors for pemetrexed toxicity include high-dose oncology regimens, impaired renal function, and concurrent use of nephrotoxic medications. PATIENT MANAGEMENT: For patients receiving pemetrexed, consider discontinuation of proton pump inhibitors for the duration of pemetrexed therapy. If concurrent use cannot be avoided, monitor closely for elevated pemetrexed levels and toxicity. DISCUSSION: A prospective observational study of 156 patients receiving pemetrexed-based therapy found that severe hematological toxicity, namely neutropenia and anemia, occurred in 34/55 patients (61.8%) taking concurrent proton pump inhibitors (PPIs) and in 36/101 patients (35.6%) who did not consume PPIs. In Cox regression multivariable analysis, the hazard ratio for severe hematological toxicity with PPI use was 2.51 (95% CI = 1.47-4.26). Esomeprazole, pantoprazole, and lansoprazole were the most consumed PPIs in the study, but no correlation was investigated.(1) A retrospective review of 61 patients investigated medication-related causes of severe hematological toxicity in patients on pemetrexed/carboplatin chemotherapy. Twenty-three patients took PPIs: lansoprazole (n=16), esomeprazole (n=5), omeprazole (n=1), and rabeprazole (n=1). In a multiple logistic regression analysis, use of PPIs in patients receiving pemetrexed/carboplatin combination chemotherapy was associated severe hematotoxicity (odds ratio: 5.34, 95% CI: 1.06-26.94, P = 0.042).(2) In an in vitro analysis and retrospective study, lansoprazole, rabeprazole, pantoprazole, esomeprazole, omeprazole, and vonoprazan were shown to inhibit OAT3-mediated uptake of pemetrexed, with lansoprazole having the greatest inhibitory effect. In the multivariate analysis of 108 patients, concurrent use of lansoprazole (but not other PPIs) and pemetrexed/carboplatin was a significant risk factor for the development of hematological toxicity (odds ratio: 10.004, P = 0.005).(3) In a retrospective study of 74 patients who received pemetrexed, 24 patients (32%) were on concomitant PPIs. Pemetrexed toxicity was associated with cystatin clearance (p=0.0135), albumin level (p=0.0333), and proton pump inhibitors (p=0.035) on multivariate analysis. Most patients (n=14) took esomeprazole or omeprazole, with the remainder taking lansoprazole (n=5), pantoprazole (n=4) or an unspecified agent.(4) |
ALIMTA, AXTLE, PEMETREXED, PEMETREXED DISODIUM, PEMFEXY, PEMRYDI RTU |
| Sparsentan/H2 Antagonists; Proton Pump Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The aqueous solubility of sparsentan is pH dependent. Higher gastric pH leads to lower solubility. H2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) increase gastric pH and may decrease the absorption of sparsentan.(1) CLINICAL EFFECTS: Coadministration of H2RAs or PPIs may reduce the bioavailability of sparsentan, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of sparsentan with PPIs and H2RAs should be avoided.(1) DISCUSSION: Sparsentan is practically insoluble in water but has intrinsic solubility of 1.48 mg/mL and 0.055 mg/mL below pH 1.2 and 6.8, respectively. H2RAs and PPIs raise gastric pH and may impair dissolution and absorption of sparsentan.(1) |
FILSPARI |
| Nirogacestat/H2 Antagonists; Proton Pump Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The aqueous solubility of nirogacestat is pH dependent. Higher gastric pH leads to lower solubility which may reduce nirogacestat absorption.(1) CLINICAL EFFECTS: Coadministration of proton pump inhibitors (PPIs) or H2 antagonists may reduce the bioavailability of nirogacestat, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of nirogacestat with proton pump inhibitors, H2 antagonists, and antacids should be avoided. If coadministration with an acid-reducing agent is unavoidable, take nirogacestat 2 hours before or 2 hours after a locally acting antacid.(1) DISCUSSION: The solubility of nirogacestat is poor at a pH >= 6.(1) Concomitant use of proton pump inhibitors, H2 antagonists, or antacids are expected to reduce concentrations of nirogacestat.(1) |
OGSIVEO |
There are 7 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Itraconazole; Ketoconazole/Agents Affecting Gastric pH SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Antacids, buffers in didanosine products, H2 antagonists, and proton-pump inhibitors increase the stomach pH. Quinapril tablets may contain a high percentage of magnesium. Since some orally administered azole antifungal agents require an acidic medium for optimal absorption, agents may decrease the absorption of azole antifungal agents. CLINICAL EFFECTS: Simultaneous administration of an antacid, buffered didanosine, a H2 antagonist, or a proton-pump inhibitor may result in decreased therapeutic effects of the azole antifungal. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If the concurrent administration of these two agents cannot be avoided, consider administering two capsules of glutamic acid hydrochloride 15 minutes before administering the antifungal and separate the administration times of the antifungal and the agent affecting gastric pH by at least two hours. DISCUSSION: Itraconazole, ketoconazole, and posaconazole require an acidic medium for predictable dissolution and absorption decreases as pH increases and proton pump inhibitors are expected to decrease their absorption.(1-4) In a study in 11 healthy subjects, omeprazole (40 mg daily) decreased the maximum concentration (Cmax) and area-under-curve (AUC) of itraconazole (200 mg single dose) by 66% and 64%, respectively.(5) In a study in 15 healthy subjects, omeprazole (40 mg daily) had no effect on the pharmacokinetics of itraconazole solution.(6) In a study in 9 healthy subjects, omeprazole (60 mg) decreased the AUC of ketoconazole (200 mg single dose) by 83.4% compared to control (ketoconazole alone). Administration of Coca-Cola (240 ml) with ketoconazole and omeprazole raised ketoconazole AUC to 65% of control values.(7) Omeprazole has been shown to have no significant effect on the absorption of fluconazole(8) or voriconazole.(9) Case reports and in-vivo studies have documented significant decreases in ketoconazole levels during concurrent therapy with H-2 antagonists, including cimetidine and ranitidine. Concurrent administration of itraconazole and famotidine resulted in a significant decrease in itraconazole levels, but no significant changes in famotidine levels. An interaction should be expected to occur between both ketoconazole or itraconazole and the other H-2 antagonists.(10-14) In randomized, open-labeled, cross-over study in 12 healthy subjects, simultaneous administration of an antacid decreased the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of itraconazole (200 mg) by 66% and 70%, respectively. Time to Cmax (Tmax) increased by 70%.(15) This interaction has also been reported in a case report.(16) In a study in 3 subjects, simultaneous administration of a combination aluminum hydroxide/magnesium hydroxide (30 ml) decreased the AUC of a single dose of ketoconazole (200 mg) by 41%.(172) In a case report, a patient receiving concurrent ketoconazole with aluminum hydroxide, cimetidine, and sodium bicarbonate did not respond to therapy until cimetidine was discontinued and the administration time of aluminum hydroxide and cimetidine was changed to 2 hours after ketoconazole. In a follow-up study in 2 subjects, concurrent cimetidine and sodium hydroxide lowered ketoconazole levels.(18) In a study in 14 subjects, simultaneous administration of aluminum hydroxide/magnesium hydroxide (20 ml, 1800 mg/1200 mg) had no significant effects on fluconazole pharmacokinetics.(3) In a randomized, open-label, cross-over study in 6 subjects, simultaneous administration of itraconazole with buffered didanosine tablets resulted in undetectable levels of itraconazole.(19) In a randomized cross-over study in 12 HIV-positive subjects, administration of buffered didanosine tablets 2 hours after ketoconazole had no effects on ketoconazole levels.(20) In a randomized, cross-over, open-label study in 24 healthy subjects, simultaneous administration of enteric-coated didanosine had no effect on ketoconazole pharmacokinetics.(21) One or more of the drug pairs linked to this monograph have been included in a list of interactions that could be considered for classification as "non-interruptive" in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology. |
ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KETOCONAZOLE, SPORANOX, TOLSURA |
| Omeprazole; Pantoprazole/Voriconazole SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Voriconazole is a strong CYP3A4 inhibitor and a moderate inhibitor of CYP2C19. Omeprazole and pantoprazole are predominantly metabolized by CYP2C19 but are also a substrate of CYP3A4. Voriconazole may inhibit the metabolism of omeprazole and pantoprazole by CYP2C19 and CYP3A4.(1-3) CLINICAL EFFECTS: The concurrent use of voriconazole and either omeprazole or pantoprazole may result in elevated levels of omeprazole and pantoprazole, and increase the risk of proton pump inhibitor (PPI) related side effects including gastroenteritis, Clostridioides difficile associated diarrhea, fractures, hypomagnesemia and vitamin B12 deficiency.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of voriconazole states that when voriconazole is initiated in patients receiving dosages of omeprazole of 40 mg/day or greater, the dosage of omeprazole should be reduced by one-half.(1) The manufacturer of voriconazole states concurrent use of other proton pump inhibitors (PPIs) that are CYP2C19 substrates such as pantoprazole may also require a dose adjustment.(1) DISCUSSION: In healthy subjects, concurrent voriconazole (400 mg every 12 hours Day 1, 200 mg Days 2-7) with omeprazole (40 mg daily for Days 1-7) increased the maximum concentration (Cmax) and area-under-curve (AUC) of omeprazole by 2-fold and 4-fold, respectively. Therefore, the manufacturer of voriconazole recommends that when voriconazole is initiated in patients receiving dosages of omeprazole of 40 mg/day or greater, the dosage of omeprazole should be reduced by one-half.(1) In healthy subjects, concurrent voriconazole (400 mg every 12 hours Day 1, 200 mg Days 2-10) with omeprazole (40 mg once daily) increased the Cmax and AUC of voriconazole by 15% and 40%, respectively. The manufacturer of voriconazole does not recommend a dosage adjustment of voriconazole when administered with omeprazole.(1) |
VFEND, VFEND IV, VORICONAZOLE |
| Amphetamines/H2 Antagonists; Proton Pump Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: H2 antagonists and proton pump inhibitors (PPIs) may alter the timing of absorption of amphetamines. CLINICAL EFFECTS: Concurrent use of amphetamines and H2 antagonists or PPIs may result in an increased absorption rate and a change in timing of peak amphetamine levels. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer states that patients receiving concurrent amphetamines and H2 antagonists or PPIs should be monitored for changes in the timing and clinical effects of amphetamines.(1) Monitor patients receiving concurrent therapy for changes in amphetamine effectiveness and side effects. The Canadian manufacturer states that concurrent use of proton pump inhibitors and amphetamines should be avoided.(3) DISCUSSION: During concurrent use of a proton pump inhibitor, the median time to maximum concentration (Tmax) of Adderall XR decreased from 5 hours to 2.75 hours.(3) In a 4-way crossover study in healthy subjects, omeprazole had no effect on the total exposure a single dose of mixed amphetamine salts (20 mg); however median Tmax decreased from 5 hours to 2.75 hours. Approximately 50% of subjects had a decrease in Tmax of equal to or greater than 1 hour.(4) |
ADDERALL, ADDERALL XR, ADZENYS XR-ODT, AMPHETAMINE SULFATE, DESOXYN, DEXEDRINE, DEXTROAMPHETAMINE SULFATE, DEXTROAMPHETAMINE SULFATE ER, DEXTROAMPHETAMINE-AMPHET ER, DEXTROAMPHETAMINE-AMPHETAMINE, DYANAVEL XR, EVEKEO, METHAMPHETAMINE HCL, MYDAYIS, PROCENTRA, ZENZEDI |
| Methotrexate(low strength inj, oral)/Proton Pump Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Proton pump inhibitors(PPIs) may inhibit the active secretion of methotrexate from the kidney via inhibition of the hydrogen-potassium ATPase(1) and may reduce uptake of methotrexate into breast cancer resistance protein via competitive inhibition.(2,3) CLINICAL EFFECTS: The concurrent use of methotrexate and proton pump inhibitors may result in elevated levels of methotrexate and increased methotrexate-related adverse effects and toxicities, leading to increased risk of severe neurotoxicity, stomatitis, and myelosuppression, including neutropenia.(1-7,9) PREDISPOSING FACTORS: High dose methotrexate therapy appears to increase the risk for and severity of this interaction.(4,9) PATIENT MANAGEMENT: Patients receiving concurrent use of methotrexate and proton pump inhibitors should be monitored closely for elevated methotrexate levels and methotrexate toxicity. The US manufacturer of omeprazole states that secretory ability returns gradually over three to five days following discontinuation.(4) This interaction has best described in patients receiving high dose methotrexate for cancer treatment. Therefore, it would seem prudent to discontinue proton pump inhibitors several days prior to high dose methotrexate therapy. The magnitude and frequency of this interaction in patients receiving less than or equal to 15 mg weekly is less clear. While a small study suggested lansoprazole was safe in rheumatoid arthritis patients taking 7.5 - 15 mg weekly(8), at least one case report of PPI associated methotrexate toxicity at a low dose (15 mg IM weekly) has been described.(7) DISCUSSION: In a clinical trial in 74 patients on high dose (1-5 G/m2) methotrexate therapy, data was examined to determine if proton pump inhibitor (omeprazole, pantoprazole, rabeprazole) use affects methotrexate elimination. Delayed elimination was found to be more frequent in those with co-administration of a proton pump inhibitor (31.7% vs. 13.8%), resulting in higher plasma methotrexate concentrations at 24, 48, and 74 hours. The effect was seen with lansoprazole, omeprazole, pantoprazole, and rabeprazole.(2) There are three case reports(1,5,6) of elevated methotrexate levels or delayed methotrexate elimination resulting from concurrent administration of high dose methotrexate and omeprazole, including one patient(6) that developed severe mucositis. In each case, omeprazole was discontinued and normal methotrexate kinetics were observed on subsequent cycles with no further adverse effects noted. In a case report of a 59 year-old male on low dose (15 mg weekly) methotrexate, administration of pantoprazole (20 mg daily) was found to increase the AUC of the metabolite 7-hydroxymethotrexate by 70%.(7) In a manufacturer sponsored clinical trial, 28 adults with rheumatoid arthritis on low dose (7.5-15 mg weekly) methotrexate were assigned to receive lansoprazole (30 mg daily) and naproxen (500 mg twice daily) on Days 1-7 of therapy. The half life of the metabolite 7-hydroxymethotrexate was prolonged with concurrent administration, but no other statistically significant differences were found in regards to the plasma concentration profiles of methotrexate or 7-hydroxymethotrexate.(8) |
JYLAMVO, METHOTREXATE, OTREXUP, RASUVO, TREXALL, XATMEP |
| Mycophenolate Mofetil/Proton Pump Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown. One theory is that proton pump inhibitors may prevent mycophenolate mofetil from being converted to mycophenolic acid in the gastrointestinal tract.(1-5) CLINICAL EFFECTS: Concurrent use of proton pump inhibitors (PPIs) may result in decreased mycophenolic acid levels and effects, including increased risk of transplant rejection. PREDISPOSING FACTORS: Other factors which may affect systemic mycophenolate exposure include renal function, serum albumin, gender, race, the choice of calcineurin inhibitor (CNI), and use of other drugs which inhibit absorption or enterohepatic recirculation of mycophenolate. PATIENT MANAGEMENT: If concurrent treatment of mycophenolate mofetil and a PPI is needed, evaluate predisposing risk factors (e.g. renal function, gender, race, and presence of other interacting drugs) which may increase or decrease mycophenolate exposure. If a patient is at risk for low mycophenolic acid levels, options may include converting to delayed release mycophenolic acid (mycophenolate sodium) which is not susceptible to this interaction (4,8,9), or monitoring mycophenolic acid levels to assure therapeutic concentrations are attained. DISCUSSION: A study compared 21 heart transplant patients maintained on mycophenolate mofetil and pantoprazole (40 mg daily) to 12 patients maintained on mycophenolate without pantoprazole. There was no significant difference in mycophenolate dose between the groups. However, mycophenolic acid levels at 30 minutes, 1 hour, 2 hours, and 12 hours were significantly lower in patients who received pantoprazole (63%, 44%, 34%, 52%, respectively). Mycophenolic acid area-under-curve (AUC) and maximum concentration (Cmax) were also significantly lower in patients who received pantoprazole (30% and 78%, respectively). There was a trend for more acute rejection episodes and transplant vasculopathy in patients receiving pantoprazole.(1) A study compared 23 patients with autoimmune diseases maintained on mycophenolate mofetil and pantoprazole (40 mg daily) to 13 patients maintained on mycophenolate without pantoprazole. There was no significant difference in mycophenolate dose between the groups. The AUC and Cmax of mycophenolic acid decreased by 37% and 60%, respectively, in patients treated with pantoprazole. The activity of mycophenolic acid decreased by 42% in patients receiving pantoprazole.(2) In a study in 22 heart transplant patients receiving mycophenolate mofetil (1000 mg twice daily), mycophenolic acid levels at 30 and 60 minutes post-dose were 55% and 37% lower, respectively, when patients were receiving pantoprazole (40 mg daily). The AUC and Cmax of mycophenolic acid were both 41% when patients were receiving pantoprazole. The time to reach Cmax (Tmax) was 29% longer.(3) A study in 12 healthy subjects compared the effects of pantoprazole (40 mg twice daily) on single doses of mycophenolate mofetil (1000 mg) and enteric-coated mycophenolate sodium (720 mg). Pantoprazole decreased the Cmax and AUC of mycophenolic acid following mycophenolate mofetil administration by 57% and 27%, respectively. There were no effects on mycophenolate acid following mycophenolate sodium administration.(4) A study in renal transplant patients, patients receiving mycophenolate mofetil and tacrolimus without PPI therapy (n=22) were compared to patients receiving concurrent mycophenolate mofetil, tacrolimus, and lansoprazole (30 mg, n=22) and patients receiving concurrent mycophenolate mofetil, tacrolimus, and rabeprazole (10 mg, n=17). Mycophenolic acid Cmax, dose-adjusted Cmax, and AUC(0-6h) were significantly lower in patients receiving lansoprazole when compared to patients not receiving PPI therapy. There were no significant differences between patients receiving rabeprazole and those not receiving PPI therapy; however, rabeprazole acid lowering effects are lower than lansoprazole.(5) A cross-sectional, retrospective analysis of renal transplant patients on omeprazole, mycophenolate, and a calcineurin inhibitor found that in the first week post-transplant the mycophenolate active moiety levels were reduced to a point of clinical significance. However, after that first week, the effect seemed to be less clinically significant.(6) In a study of heart transplant patients, use of pantoprazole (20 mg to 80 mg daily) significantly reduced the AUC of mycophenolic acid produced from a mean daily dose of 2.2+/-0.8 mycophenolate mofetil (p=0.02). However, mycophenolic acid minimum concentration (Cmin) was not significantly different.(7) In a study in healthy subjects, the Cmax and AUC of mycophenolic acid were decreased when mycophenolate mofetil was administered with omeprazole (20 mg BID); however, there was no effect on the Cmax or AUC of mycophenolic acid when enteric-coated mycophenolate mofetil was administered with omeprazole.(8) In a study in heart or lung transplant patients, concurrent pantoprazole had no effect on the Cmax, Tmax, or AUC of mycophenolic acid following administration of enteric-coated mycophenolate sodium. Additionally no significant difference of inosine 5?-monophosphate dehydrogenase (IMPDH) activity was seen with EC-mycophenolate given alone or with pantoprazole.(9) In a subanalysis of the CLEAR Study, there were no significant effects of omeprazole or pantoprazole on mycophenolic acid levels in the study group randomized to received intensified dosing with mycophenolate mofetil (1.5 g BID for 5 days, then 1 g BID).(10) |
CELLCEPT, MYCOPHENOLATE MOFETIL, MYHIBBIN |
| Belumosudil/Proton Pump Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Belumosudil is best absorbed in an acidic environment. Proton pump inhibitors (PPIs) decrease gastric acidity and may decrease belumosudil absorption and systemic concentrations.(1) CLINICAL EFFECTS: Coadministration of PPIs with belumosudil decreases systemic concentrations of belumosudil, which may decrease the efficacy of belumosudil.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Increase the dosage of belumosudil to 200 mg twice daily when coadministered with PPIs.(1) DISCUSSION: Coadministration of rabeprazole decreased belumosudil maximum concentration (Cmax) by 87% and area-under-curve (AUC) by 80%, and omeprazole decreased belumosudil Cmax by 68% and AUC by 47% in healthy subjects.(1) |
REZUROCK |
| Palbociclib/Proton Pump Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The mechanism of this interaction is not fully understood and may involve dysbiosis or gastric pH changes resulting from proton pump inhibitors (PPIs).(1,2) The aqueous solubility of palbociclib is pH-dependent. Higher gastric pH leads to lower solubility which may reduce palbociclib absorption.(1) CLINICAL EFFECTS: Coadministration of PPIs may reduce the bioavailability of palbociclib, leading to decreased systemic levels and effectiveness.(1) Although administration of palbociclib with food minimizes the decrease in absorption,(1) retrospective studies and a meta-analysis have found lower survival rates among patients on concurrent PPIs.(2-7) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of palbociclib capsules states that palbociclib should be taken with food, whereas palbociclib tablets may be taken with or without food. There are no constraints on concurrent use of proton pump inhibitors.(1) Given the decreased survival rates observed in patients who received PPIs with palbociclib, the authors of some studies on concurrent use of these agents have made various recommendations, including avoiding PPIs with palbociclib, using ribociclib instead of palbociclib, using low strengths of PPIs, or using H2-antagonists or antacids.(2-7) DISCUSSION: Palbociclib solubility decreases significantly above pH 4.(1) In a study with healthy volunteers, rabeprazole decreased the maximum concentration (Cmax) and area-under-curve (AUC) of single-dose palbociclib without food by 80% and 62%, respectively. In another study of healthy volunteers in a fed state, rabeprazole decreased Cmax and AUC of single-dose palbociclib by 41% and 13%, respectively.(1) A systematic review and meta-analysis examined studies of HER2-negative, hormone receptor-positive patients with metastatic breast cancer treated with palbociclib or ribociclib with or without concomitant PPIs that reported on survival outcomes. Eight studies consisting of 2,584 patients (830 on PPIs, 1754 not on PPIs) were included. Patients on concurrent PPIs had a significantly higher risk of all-cause mortality (HR, 2.03; 95% CI, 1.49 to 2.77) and disease progression (HR, 1.75; 95% CI, 1.26 to 2.43) compared to patients not on PPIs, though there was a high degree of heterogeneity in disease progression.(2) A retrospective cohort of patients with advanced or metastatic breast cancer treated with palbociclib capsules (344 patients on PPIs, 966 patients not on PPIs) revealed that patients on PPIs had shorter progression-free survival (PFS) (HR 1.76 (95% CI, 1.46-2.13) and lower overall survival (HR, 2.71 [95% CI, 2.07-3.53]).(3) A post-hoc analysis of the phase 2 PARSIFAL trial evaluated PFS in patients on palbociclib capsules. 326 patients were PPI-naive, 64 patients were early users of PPIs (started on PPIs since starting palbociclib), and 91 patients were long-term users of PPIs. PPI use was associated with a shorter PFS (HR in early PPI users 1.5; 95% CI 1.1-2.2; HR in long-term PPI users 1.4; 95% CI 1.1-1.9).(4) A retrospective study of 50 patients with metastatic breast cancer on palbociclib found that concurrent PPI use was associated with a shorter PFS.(5) In an observational study of patients with metastatic breast cancer on palbociclib capsules, PFS was compared between 65 patients on PPIs and 40 patients not on PPIs. On multivariate analysis, PPI usage was an independent predictor of shorter PFS (HR 5.60; 95% confidence interval: 1.98-15.85).(6) A retrospective observational cohort of metastatic breast cancer patients on palbociclib found that patients on concurrent PPIs had a shorter PFS than those not on PPIs (14.0 versus 37.9 months, p < 0.0001).(7) In contrast to these findings, other studies have not found a detrimental effect of PPIs on palbociclib efficacy. A retrospective observational study focused on 112 patients with endocrine-resistant metastatic breast cancer on palbociclib capsules (n=58) and tablets (n=20). There was no difference in PFS in patients on concurrent PPIs compared to those not on PPIs.(8) A study looking at 82 patients with metastatic breast cancer treat 1st line with palbociclib tablets(9) and a retrospective observational study on metastatic breast cancer patients on palbociclib capsules(10) also did not find a significantly different PFS between patients with and without concurrent PPIs. |
IBRANCE |
The following contraindication information is available for PROTONIX IV (pantoprazole sodium):
Drug contraindication overview.
Known hypersensitivity to pantoprazole, any other ingredient in the formulation, or other substituted benzimidazoles (e.g., esomeprazole, lansoprazole, omeprazole, rabeprazole).
Known hypersensitivity to pantoprazole, any other ingredient in the formulation, or other substituted benzimidazoles (e.g., esomeprazole, lansoprazole, omeprazole, rabeprazole).
There are 0 contraindications.
There are 4 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Clostridioides difficile infection |
| Interstitial nephritis |
| Subacute cutaneous lupus erythematosus |
| Systemic lupus erythematosus |
There are 5 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| CYp2c19 poor metabolizer |
| Fracture |
| Hypomagnesemia |
| Osteoporosis |
| Vitamin b12 deficiency |
The following adverse reaction information is available for PROTONIX IV (pantoprazole sodium):
Adverse reaction overview.
Adverse effects occurring in more than 2% of patients receiving oral pantoprazole and reported more frequently with pantoprazole than with placebo include headache, diarrhea, abdominal pain, vomiting, flatulence, dizziness, and arthralgia. Adverse effects occurring in more than 1% of patients receiving IV pantoprazole and that generally had an unclear relationship to the drug include headache, injection site reaction (including thrombophlebitis and abscess), abdominal pain, constipation, dyspepsia, nausea, diarrhea, insomnia, dizziness, and rhinitis.
Adverse effects occurring in more than 2% of patients receiving oral pantoprazole and reported more frequently with pantoprazole than with placebo include headache, diarrhea, abdominal pain, vomiting, flatulence, dizziness, and arthralgia. Adverse effects occurring in more than 1% of patients receiving IV pantoprazole and that generally had an unclear relationship to the drug include headache, injection site reaction (including thrombophlebitis and abscess), abdominal pain, constipation, dyspepsia, nausea, diarrhea, insomnia, dizziness, and rhinitis.
There are 27 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. | None. |
| Rare/Very Rare |
|---|
|
Abnormal hepatic function tests Acute generalized exanthematous pustulosis Agranulocytosis Anaphylaxis Angioedema Clostridioides difficile infection DRESS syndrome Erythema multiforme Fracture Hepatic failure Hepatitis Hepatocellular damage Hypersensitivity drug reaction Hypocalcemia Hypokalemia Hyponatremia Interstitial nephritis Jaundice Leukopenia Pancytopenia Rhabdomyolysis Stevens-johnson syndrome Subacute cutaneous lupus erythematosus Systemic lupus erythematosus Thrombocytopenic disorder Thrombophlebitis Toxic epidermal necrolysis |
There are 34 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Acute abdominal pain Arthralgia Diarrhea Dizziness Flatulence Headache disorder Nausea Vomiting |
None. |
| Rare/Very Rare |
|---|
|
Acute cognitive impairment Benign fundic gland polyposis of stomach Blurred vision Constipation Drowsy Dysgeusia Erectile dysfunction Facial edema Fatigue Fever General weakness Hallucinations Hypertriglyceridemia Hypomagnesemia Increased creatine kinase level Injection site sequelae Insomnia Loss of taste Malaise Myalgia Pruritus of skin Skin photosensitivity Skin rash Urticaria Vertigo Xerostomia |
The following precautions are available for PROTONIX IV (pantoprazole sodium):
Efficacy and safety of oral pantoprazole for short-term treatment of erosive esophagitis associated with GERD in pediatric patients 1-16 years of age are supported by controlled clinical trials in adults and additional safety, efficacy, and pharmacokinetic studies in pediatric patients. However, because an appropriate dosage formulation is not available for children younger than 5 years of age, oral pantoprazole is labeled for use only in children 5 years of age or older. Safety and efficacy of oral pantoprazole for uses other than treatment of erosive esophagitis have not been established in pediatric patients.
Oral pantoprazole was evaluated in several clinical trials in pediatric patients 1-16 years of age with endoscopically diagnosed or symptomatic GERD, including a limited number of patients with endoscopically diagnosed erosive esophagitis. Because these clinical trials had no placebo or active comparator group and provided no evidence of a dose-related response to the pantoprazole dosages studied, the results were inconclusive regarding efficacy of pantoprazole for the treatment of symptomatic GERD in pediatric patients. Adverse effects reported in more than 4% of patients included upper respiratory tract infection, headache, fever, diarrhea, vomiting, rash, and abdominal pain.
Following oral administration of a single 40-mg dose of pantoprazole, exposure to the drug was about 39% higher in children 6-11 years of age and about 10% higher in adolescents 12-16 years of age compared with adults. Efficacy of oral pantoprazole in infants younger than 1 year of age has not been established. In a treatment-withdrawal study in infants 1-11 months of age with symptomatic GERD, pantoprazole was not more effective than placebo. Safety and efficacy of IV pantoprazole in pediatric patients have not been established.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Oral pantoprazole was evaluated in several clinical trials in pediatric patients 1-16 years of age with endoscopically diagnosed or symptomatic GERD, including a limited number of patients with endoscopically diagnosed erosive esophagitis. Because these clinical trials had no placebo or active comparator group and provided no evidence of a dose-related response to the pantoprazole dosages studied, the results were inconclusive regarding efficacy of pantoprazole for the treatment of symptomatic GERD in pediatric patients. Adverse effects reported in more than 4% of patients included upper respiratory tract infection, headache, fever, diarrhea, vomiting, rash, and abdominal pain.
Following oral administration of a single 40-mg dose of pantoprazole, exposure to the drug was about 39% higher in children 6-11 years of age and about 10% higher in adolescents 12-16 years of age compared with adults. Efficacy of oral pantoprazole in infants younger than 1 year of age has not been established. In a treatment-withdrawal study in infants 1-11 months of age with symptomatic GERD, pantoprazole was not more effective than placebo. Safety and efficacy of IV pantoprazole in pediatric patients have not been established.
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Category B. (See Users Guide.)
Pantoprazole is distributed into milk; discontinue nursing or the drug because of potential risk in nursing infants.
There are no substantial differences in safety and efficacy relative to younger adults. No dosage adjustment is necessary in geriatric patients.
The following prioritized warning is available for PROTONIX IV (pantoprazole sodium):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for PROTONIX IV (pantoprazole sodium)'s list of indications:
| Erosive esophagitis | |
| K21.0 | Gastro-esophageal reflux disease with esophagitis |
| K21.00 | Gastro-esophageal reflux disease with esophagitis, without bleeding |
| K21.01 | Gastro-esophageal reflux disease with esophagitis, with bleeding |
| K22.1 | Ulcer of esophagus |
| K22.10 | Ulcer of esophagus without bleeding |
| K22.11 | Ulcer of esophagus with bleeding |
| Gastric hypersecretion with systemic mastocytosis | |
| C96.21 | Aggressive systemic mastocytosis |
| D47.02 | Systemic mastocytosis |
| K31.89 | Other diseases of stomach and duodenum |
| Gastroesophageal reflux disease | |
| K21 | Gastro-esophageal reflux disease |
| K21.0 | Gastro-esophageal reflux disease with esophagitis |
| K21.00 | Gastro-esophageal reflux disease with esophagitis, without bleeding |
| K21.9 | Gastro-esophageal reflux disease without esophagitis |
| Pathological gastric acid hypersecretory condition | |
| K31.89 | Other diseases of stomach and duodenum |
| Zollinger-ellison syndrome | |
| E16.4 | Increased secretion of gastrin |
Formulary Reference Tool