Gastrointestinal

Pepticare 40 (Pantoprazole)


Pharmacologic Category

Proton Pump Inhibitor; Substituted Benzimidazole

Dosing: Adult

Erosive esophagitis associated with GERD:

Oral:

Treatment: 40 mg once daily for up to 8 weeks; an additional 8 weeks may be used in patients who have not healed after an 8-week course. Note: Canadian labeling recommends initial treatment for up to 4 weeks and an additional 4 weeks in patients who have not healed after the initial 4-week course. Lower doses (20 mg once daily) have been used successfully in mild GERD treatment (Dettmer, 1998).

Maintenance of healing: 40 mg once daily (US labeling) or 20 to 40 mg once daily (Canadian labeling); 20 mg once daily has been used successfully in maintenance of healing (Escourrou, 1999). Note: Has not been studied beyond 12 months.

IV: 40 mg once daily for 7 to 10 days

Pathological hypersecretory conditions, including Zollinger-Ellison syndrome:

Oral: Initial: 40 mg twice daily; adjust dose based on patient needs; doses up to 240 mg daily have been administered

IV: 80 mg every 12 hours; adjust dose based on acid output measurements; 160 to 240 mg daily in divided doses has been used for a limited period (up to 7 days)

Prevention of rebleeding in peptic ulcer bleed (off-label use): IV:

Continuous infusion: Loading dose of 80 mg, followed by 8 mg/hour infusion for 72 hours (Barkun, 2010; Zargar, 2006).

Intermittent dosing: Loading dose of 80 mg followed by either 40 mg every 12 hours for 72 hours (Hung, 2007; Yamada, 2012) or 40 mg every 6 hours for 72 hours (Hsu, 2009). May also administer 40 mg every 12 hours for 72 hours without a loading dose (Yuksel, 2008).

Note: After completion, continue therapy with a single daily-dose oral PPI for a duration dictated by the underlying etiology (Barkun, 2010).

Helicobacter pylori eradication (off-label use in US): Oral:

American College of Gastroenterology guidelines (Chey, 2007):

Nonpenicillin allergy: 40 mg twice daily administered with amoxicillin 1000 mg and clarithromycin 500 mg twice daily for 10 to 14 days

Penicillin allergy: 40 mg twice daily administered with clarithromycin 500 mg and metronidazole 500 mg twice daily for 10 to 14 days or 40 mg once or twice daily administered with bismuth subsalicylate 525 mg and metronidazole 250 mg plus tetracycline 500 mg 4 times daily for 10 to 14 days

Canadian labeling: 40 mg twice daily administered with clarithromycin 500 mg twice daily and either metronidazole 500 mg or amoxicillin 1,000 mg twice daily for 7 days

Peptic ulcer disease (Canadian labeling): Oral: Treatment: 40 mg once daily for 2 weeks (duodenal ulcer) or 4 weeks (gastric ulcer); may extend therapy for an additional 2 or 4 weeks (based on indication) for inadequate healing

NSAID-induced ulcer prophylaxis (Canadian labeling): Oral: 20 mg once daily

Symptomatic GERD (Canadian labeling): Oral: Treatment: 40 mg once daily for up to 4 weeks; failure to achieve adequate symptom relief after the initial 4 weeks of therapy warrants further evaluation

Erosive esophagitis associated with GERD:

Oral:

Children <5 years: Dosage not established.

Children ≥5 years: Note: Consider a dose reduction in known CYP2C19 poor metabolizers.

≥15 to <40 kg: 20 mg once daily for up to 8 weeks

≥40 kg: 40 mg once daily for up to 8 weeks

IV: Dosage not established

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

US labeling: No dosage adjustment necessary; pantoprazole is not removed by hemodialysis.

Canadian labeling: Use is not recommended in combination therapy of Helicobacter pylori in patients with severe renal impairment (has not been studied).

Dosing: Hepatic Impairment

US labeling: No dosage adjustment necessary; doses >40 mg daily have not been evaluated.

Canadian labeling:

Mild-moderate impairment: No dosage adjustment necessary.

Severe impairment: IV, Oral: Manufacturer labeling suggests a maximum dose of 20 mg daily. Use in combination therapy of Helicobacter pylori is not recommended in patients with severe hepatic impairment (has not been studied).

Dosage Forms

Solution Reconstituted, Intravenous:

Panto IV: 40 mg [contains edetate disodium]

Administration

IV: Flush IV line before and after administration. In-line filter not required.

2-minute infusion: The volume of reconstituted solution (4 mg/mL) may be administered intravenously over at least 2 minutes.

15-minute infusion: Infuse over 15 minutes at a rate not to exceed 7 mL/minute (3 mg/minute).

Continuous infusion: May also be administered as a continuous infusion for the prevention of rebleeding with in peptic ulcer bleed (off-label use).

IV infusion: 80 mg in 100 mL (concentration: 0.8 mg/mL) of D5W or NS

Use

IV:

Gastroesophageal reflux disease associated with a history of erosive esophagitis: Short-term treatment (7 to 10 days) of adult patients with gastroesophageal reflux disease (GERD) and a history of erosive esophagitis.

Pathological hypersecretion associated with Zollinger-Ellison syndrome: Treatment of adult patients with pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

Canadian labeling: Additional use (not in US labeling): Oral: Peptic ulcer disease (eg, duodenal or gastric ulcer); adjunct treatment with antibiotics for Helicobacter pylori eradication; NSAID-induced ulcer prophylaxis (Pantoloc)

Use: Off-Label

Prevention of rebleeding in peptic ulcer bleed; Stress ulcer prophylaxis in the critically ill; Adjunct treatment with antibiotics for Helicobacter pylori eradication

Adverse Reactions

>10%: Central nervous system: Headache (adults 12%; children >4%)

1% to 10%:

Cardiovascular: Facial edema (≤4%), edema (≤2%)

Central nervous system: Dizziness (≤4%), vertigo (≤4%), depression (≤2%)

Dermatologic: Skin rash (adults ≤2%; children >4%), urticaria (≤4%), pruritus (≤2%), skin photosensitivity (≤2%)

Endocrine & metabolic: Increased serum triglycerides (≤4%)

Gastrointestinal: Diarrhea (≤9%), abdominal pain (children >4%), vomiting (≥4%), constipation (≤4%), flatulence (children ≤4%), nausea (children ≤4%), xerostomia (≤2%)

Hematologic & oncologic: Leukopenia (≤2%), thrombocytopenia (≤2%)

Hepatic: Abnormal hepatic function tests (≤4%), hepatitis (≤2%)

Hypersensitivity: Hypersensitivity reaction (≤4%)

Local: Inflammation at injection site (≤2%)

Neuromuscular & skeletal: Arthralgia (≤4%), myalgia (≤4%), increased creatine phosphokinase (≤4%)

Ophthalmic: Blurred vision (≤2%)

Respiratory: Upper respiratory tract infection (children >4%)

Miscellaneous: Fever (adults ≤2%; children >4%)

<1%, postmarketing, and/or case reports: Ageusia, agranulocytosis, anaphylaxis (including anaphylactic shock), angioedema, bone fracture, Clostridium difficile-associated diarrhea, confusion, contact dermatitis, cutaneous lupus erythematous, decreased libido, diabetes mellitus, drowsiness, dysgeusia, ECG abnormality, eosinophilia, erythema multiforme, esophagitis, fatigue, gastric ulcer, gastrointestinal carcinoma, hallucination, hematuria, hepatic failure, hepatotoxicity (idiosyncratic) (Chalasani 2014), hyperbilirubinemia, hypertension, hypokinesia, hypomagnesemia, hyponatremia, impotence, increased appetite, increased serum alkaline phosphatase, interstitial nephritis, ischemic heart disease, jaundice, leukocytosis, malaise, neoplasm, nervousness, optic neuropathy (including anterior ischemic), pancreatitis, pancytopenia, paresthesia, pneumonia (Eom 2011), renal disease (chronic; Lazarus 2016), rhabdomyolysis, Stevens-Johnson syndrome, systemic lupus erythematosus, thrombosis, tinnitus, tongue discoloration, toxic epidermal necrolysis, tremor, visual disturbance, weakness, weight changes

Contraindications

Hypersensitivity (eg, anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, urticaria) to pantoprazole, other substituted benzimidazole proton pump inhibitors, or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

Carcinoma: Benign and malignant neoplasia has been observed in long-term (2-year) rodent studies; while not reported in humans, the relevance of these findings in regards to tumorigenicity in humans is not known.

Clostridium difficile-associated diarrhea (CDAD): Use of proton pump inhibitors (PPIs) may increase risk of CDAD, especially in hospitalized patients; consider CDAD diagnosis in patients with persistent diarrhea that does not improve. Use the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated.

Cutaneous and systemic lupus erythematosus: Has been reported as new onset or exacerbation of existing autoimmune disease; most cases were cutaneous lupus erythematosus (CLE), most commonly, subacute CLE (occurring within weeks to years after continuous therapy). Systemic lupus erythematosus (SLE) is less common (typically occurs within days to years after initiating treatment) and occurred primarily in young adults up to elderly patients. Discontinue therapy if signs or symptoms of CLE or SLE occur and refer to specialist for evaluation; most patients improve 4 to 12 weeks after discontinuation of pantoprazole.

Fractures: Increased incidence of osteoporosis-related bone fractures of the hip, spine, or wrist may occur with proton pump inhibitor (PPI) therapy. Patients on high-dose or long-term therapy (≥1 year) should be monitored. Use the lowest effective dose for the shortest duration of time, use vitamin D and calcium supplementation, and follow appropriate guidelines to reduce risk of fractures in patients at risk.

Hypomagnesemia: Reported rarely, usually with prolonged PPI use of ≥3 months (most cases >1 year of therapy). May be symptomatic or asymptomatic; severe cases may cause tetany, seizures, and cardiac arrhythmias. Consider obtaining serum magnesium concentrations prior to beginning long-term therapy, especially if taking concomitant digoxin, diuretics, or other drugs known to cause hypomagnesemia; and periodically thereafter. Hypomagnesemia may be corrected by magnesium supplementation, although discontinuation of pantoprazole may be necessary; magnesium levels typically return to normal within 2 weeks of stopping.

Infusion-related reactions: Thrombophlebitis and serious hypersensitivity reactions, including anaphylaxis, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported with IV administration.

Interstitial nephritis: Acute interstitial nephritis has been observed in patients taking PPIs; may occur at any time during therapy and is generally due to an idiopathic hypersensitivity reaction. Discontinue if acute interstitial nephritis develops.

Vitamin B12 deficiency: Prolonged treatment (≥2 years) may lead to vitamin B12 malabsorption and subsequent vitamin B12 deficiency. The magnitude of the deficiency is dose-related and the association is stronger in females and those younger in age (<30 years); prevalence is decreased after discontinuation of therapy (Lam, 2013).

Disease-related concerns:

Gastric malignancy: Relief of symptoms does not preclude the presence of a gastric malignancy.

Gastrointestinal infection (eg, Salmonella, Campylobacter): Use of PPIs may increase risk of these infections.

Concurrent drug therapy issues:

Clopidogrel: Proton pump inhibitors (PPIs) may diminish the therapeutic effect of clopidogrel, thought to be due to reduced formation of the active metabolite of clopidogrel. The manufacturer of clopidogrel recommends either avoidance of both omeprazole (even when scheduled 12 hours apart) and esomeprazole or use of a PPI with comparatively less effect on the active metabolite of clopidogrel. Of the PPIs, pantoprazole has the lowest degree of CYP2C19 inhibition in vitro (Li, 2004) and has been shown to have less effect on conversion of clopidogrel to its active metabolite compared to omeprazole (Angiolillo, 2011). In contrast to these warnings, others have recommended the continued use of PPIs, regardless of the degree of inhibition, in patients with a history of GI bleeding or multiple risk factors for GI bleeding who are also receiving clopidogrel since no evidence has established clinically meaningful differences in outcome; however, a clinically-significant interaction cannot be excluded in those who are poor metabolizers of clopidogrel (Abraham, 2010; Levine, 2011).

Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

Edetate sodium (EDTA): Intravenous preparation contains edetate sodium; use caution in patients who are at risk for zinc deficiency if other EDTA-containing solutions are coadministered.

Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson, 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade, 1986; CDC, 1984). See manufacturer’s labeling.

Other warnings/precautions:

Appropriate use: Helicobacter pylori eradication: Short-term combination therapy (≤7 days) has been associated with a higher incidence of treatment failure. The American College of Gastroenterology recommends 10 to 14 days of therapy (triple or quadruple) for eradication of H. pylori (Chey 2007). Safety and efficacy of IV treatment for GERD and a history of erosive esophagitis beyond 10 days have not been established; transition from IV to oral therapy as soon possible.

Drug Interactions

Amphetamine: Proton Pump Inhibitors may increase the absorption of Amphetamine. Risk C: Monitor therapy

Atazanavir: Proton Pump Inhibitors may decrease the serum concentration of Atazanavir. Management: See full drug interaction monograph for details. Risk D: Consider therapy modification

Bisphosphonate Derivatives: Proton Pump Inhibitors may diminish the therapeutic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy

Bosutinib: Proton Pump Inhibitors may decrease the serum concentration of Bosutinib. Management: Consider alternatives to proton pump inhibitors, such as antacids or H2 receptor antagonists. Administer alternative agents more than 2 hours before or after bosutinib. Risk D: Consider therapy modification

Capecitabine: Proton Pump Inhibitors may diminish the therapeutic effect of Capecitabine. Risk C: Monitor therapy

Cefditoren: Proton Pump Inhibitors may decrease the serum concentration of Cefditoren. Management: If possible, avoid use of cefditoren with proton pump inhibitors (PPIs). Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of PPIs can not be avoided. Risk D: Consider therapy modification

Clopidogrel: Pantoprazole may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to the possible risk for impaired clopidogrel effectiveness, clinicians should carefully consider the need for proton pump inhibitor therapy in patients receiving clopidogrel. Other acid-lowering therapies do not appear to share this interaction. Risk D: Consider therapy modification

CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

Cysteamine (Systemic): Proton Pump Inhibitors may diminish the therapeutic effect of Cysteamine (Systemic). Risk C: Monitor therapy

Dabigatran Etexilate: Proton Pump Inhibitors may decrease serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP2C19 Substrates. Management: Seek alternatives to the CYP2C19 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Dabrafenib: Proton Pump Inhibitors may decrease the serum concentration of Dabrafenib. Dabrafenib may decrease the serum concentration of Proton Pump Inhibitors. Management: Seek alternatives to the proton pump inhibitor when possible. If concomitant therapy cannot be avoided, monitor for diminished effects of both drugs. Risk D: Consider therapy modification

Dasatinib: Proton Pump Inhibitors may decrease the serum concentration of Dasatinib. Management: Antacids (taken 2 hours before or after dasatinib administration) can be used in place of the proton pump inhibitor if some acid-reducing therapy is needed. Risk X: Avoid combination

Delavirdine: Proton Pump Inhibitors may decrease the serum concentration of Delavirdine. Management: Chronic therapy with proton pump inhibitors (PPIs) should be avoided in patients treated with delavirdine. The clinical significance of short-term PPI therapy with delavirdine is uncertain, but such therapy should be undertaken with caution. Risk X: Avoid combination

Dexmethylphenidate: Proton Pump Inhibitors may increase the absorption of Dexmethylphenidate. Specifically, proton pump inhibitors may interfere with the normal release of drug from the extended-release capsules (Focalin XR brand), which could result in both increased absorption (early) and decreased delayed absorption. Risk C: Monitor therapy

Dextroamphetamine: Proton Pump Inhibitors may increase the absorption of Dextroamphetamine. Specifically, the dextroamphetamine absorption rate from mixed amphetamine salt extended release (XR) capsules may be increased in the first hours after dosing. Risk C: Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP2C19 Substrates. Conversely, concentrations of active metabolites may be increased for those drugs activated by CYP2C19. Management: Concurrent use of enzalutamide with CYP2C19 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C19 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Erlotinib: Proton Pump Inhibitors may decrease the serum concentration of Erlotinib. Risk X: Avoid combination

Fluconazole: May increase the serum concentration of Proton Pump Inhibitors. Risk C: Monitor therapy

Gefitinib: Proton Pump Inhibitors may decrease the serum concentration of Gefitinib. Management: Avoid use of proton pump inhibitors (PPIs) with gefitinib when possible. If required, administer gefitinib 12 hours after administration of the PPI or 12 hours before the next dose of the PPI. Risk D: Consider therapy modification

Indinavir: Proton Pump Inhibitors may decrease the serum concentration of Indinavir. Risk C: Monitor therapy

Iron Salts: Proton Pump Inhibitors may decrease the absorption of Iron Salts. Exceptions: Ferric Carboxymaltose; Ferric Citrate; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Risk C: Monitor therapy

Itraconazole: Proton Pump Inhibitors may decrease the serum concentration of Itraconazole. Risk D: Consider therapy modification

Ketoconazole (Systemic): Proton Pump Inhibitors may decrease the serum concentration of Ketoconazole (Systemic). Ketoconazole (Systemic) may increase the serum concentration of Proton Pump Inhibitors. Risk D: Consider therapy modification

Ledipasvir: Proton Pump Inhibitors may decrease the serum concentration of Ledipasvir. Management: PPI doses equivalent to omeprazole 20 mg or lower may be given with ledipasvir under fasted conditions. Administration with higher doses of PPIs, 2 hours after a PPI, or in combination with food and PPIs may reduce ledipasvir bioavailability. Risk D: Consider therapy modification

Lumacaftor: May decrease the serum concentration of CYP2C19 Substrates. Risk C: Monitor therapy

Mesalamine: Proton Pump Inhibitors may diminish the therapeutic effect of Mesalamine. Proton pump inhibitor-mediated increases in gastrointestinal pH may cause the premature release of mesalamine from specific sustained-release mesalamine products. Management: Consider avoiding concurrent administration of high-dose proton pump inhibitors (PPIs) with sustained-release mesalamine products. Risk D: Consider therapy modification

Methotrexate: Proton Pump Inhibitors may increase the serum concentration of Methotrexate. Risk C: Monitor therapy

Methylphenidate: Proton Pump Inhibitors may increase the absorption of Methylphenidate. Specifically, proton pump inhibitors may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): Proton Pump Inhibitors may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, the absorption of iron may be decreased. Risk C: Monitor therapy

Mycophenolate: Proton Pump Inhibitors may decrease the serum concentration of Mycophenolate. Specifically, concentrations of the active mycophenolic acid may be reduced. Risk C: Monitor therapy

Nelfinavir: Proton Pump Inhibitors may decrease serum concentrations of the active metabolite(s) of Nelfinavir. Proton Pump Inhibitors may decrease the serum concentration of Nelfinavir. Risk X: Avoid combination

Nilotinib: Proton Pump Inhibitors may decrease the serum concentration of Nilotinib. Management: Avoid this combination when possible since separation of doses is not likely to be an adequate method of minimizing the interaction. Risk D: Consider therapy modification

PAZOPanib: Proton Pump Inhibitors may decrease the serum concentration of PAZOPanib. Risk X: Avoid combination

Posaconazole: Proton Pump Inhibitors may decrease the serum concentration of Posaconazole. Risk D: Consider therapy modification

Raltegravir: Proton Pump Inhibitors may increase the serum concentration of Raltegravir. Risk C: Monitor therapy

Rilpivirine: Proton Pump Inhibitors may decrease the serum concentration of Rilpivirine. Risk X: Avoid combination

Riociguat: Proton Pump Inhibitors may decrease the serum concentration of Riociguat. Risk C: Monitor therapy

Risedronate: Proton Pump Inhibitors may diminish the therapeutic effect of Risedronate. Proton Pump Inhibitors may increase the serum concentration of Risedronate. This applies specifically to use of delayed-release risedronate. Risk X: Avoid combination

Saquinavir: Proton Pump Inhibitors may increase the serum concentration of Saquinavir. Risk C: Monitor therapy

Tipranavir: May decrease the serum concentration of Proton Pump Inhibitors. These data are derived from studies with Ritonavir-boosted Tipranavir. Risk C: Monitor therapy

Velpatasvir: Proton Pump Inhibitors may decrease the serum concentration of Velpatasvir. Risk X: Avoid combination

Voriconazole: May increase the serum concentration of Proton Pump Inhibitors. Proton Pump Inhibitors may increase the serum concentration of Voriconazole. Management: In patients receiving omeprazole 40 mg/day or greater, reduce omeprazole dose by half when initiating voriconazole. Risk C: Monitor therapy

Food Interactions

Prolonged treatment (≥2 years) may lead to malabsorption of dietary vitamin B12 and subsequent vitamin B12 deficiency (Lam, 2013).

Pregnancy Risk Factor

B

Pregnancy Implications

Adverse events have not been observed in animal reproduction studies. Most available studies have not shown an increased risk of major birth defects following maternal use of proton pump inhibitors during pregnancy (Diav-Citrin, 2005; Erichsen, 2012; Matok, 2012; Pasternak, 2010). When treating GERD in pregnancy, PPIs may be used when clinically indicated (Katz, 2013).

Breast-Feeding Considerations

Pantoprazole is excreted in breast milk. The excretion of pantoprazole into breast milk was studied in a nursing woman, 10 months postpartum. Following a single dose of pantoprazole 40 mg, maternal milk and serum samples were obtained over 24 hours. Peak concentrations appeared in both the plasma and milk 2 hours after the dose. Pantoprazole concentrations in breast milk were below the limits of detection during most of the study period. Based on this single dose study, the authors calculated the expected exposure to a nursing infant to be 0.14% of the weight-adjusted maternal dose (Plante, 2004). Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother; however, the acidic content of the nursing infants’ stomach may potentially inactivate any ingested pantoprazole (Plante, 2004).

Dietary Considerations

IV: Due to EDTA in preparation, zinc supplementation may be needed in patients prone to zinc deficiency.

Monitoring Parameters

Hypersecretory disorders: Acid output measurements, target level <10 mEq/hour (<5 mEq/hour if prior gastric acid-reducing surgery)

Mechanism of Action

Proton pump inhibitor, suppresses gastric acid secretion by inhibiting the parietal cell H+/K+ ATP pump

Pharmacodynamics/Kinetics

Note: Pediatric patients who have the poor metabolizer genotype of CYP2C19 (CYP2C19 *2/*2) exhibited greater than a 6-fold increase in AUC compared with pediatric extensive (CYP2C19 *1/*1) and intermediate (CYP2C19 *1/*x) metabolizers. Poor metabolizers exhibited approximately 10-fold lower apparent oral clearance compared with extensive metabolizers.

Onset of action: Acid secretion: Oral: 2.5 hours; IV: 15 to 30 minutes

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