Gastroesophageal reflux disease, symptomatic: Note: Routine use is not recommended in preterm neonates (AAP [Eichenwald 2018]). Limited data available:
Preterm (PMA <44 weeks and weighing ≥1.5 kg) and Term Neonates: Oral: 2.5 mg (~1.2 mg/kg/dose) once daily administered 30 minutes prior to first feeding of the day was evaluated in a pharmacokinetic trial in 21 neonatal patients (preterm: 19; term: 2; mean GA: 28 weeks; range: 23 to 41 weeks); this dose produced slightly higher systemic exposure than adolescents and adults receiving 40 mg, but there was no evidence of accumulation with repeated administration noted; although there was a significant increase in gastric pH and the amount of time the pH >4, there was no significant difference in reflux episodes. A lower dose of 1.25 mg (0.6 mg/kg/dose) was also evaluated (n=19); however, this dose did not provide statistically significant improvements in pH-metry parameters (Kierkus 2011; Ward 2010).
Note: Dosing should be based on lean body weight in obese patients; pharmacokinetic studies suggest that obese children ≥6 years and adolescents have higher exposures and slower drug clearance compared to nonobese patients (Shakhnovich 2018; Shakhnovich 2019).
Gastroesophageal reflux disease (GERD), symptomatic (NASPGHAN/ESPGHAN [Rosen 2018]): Limited data available: Note: Guidelines recommend a 4- to 8-week treatment course; if improvement seen after 4 to 8 weeks, consider possible wean; if no response after 4 to 8 weeks, reevaluate diagnosis and consider referral to pediatric GI specialist.
Infants, Children, and Adolescents: Oral: 1 to 2 mg/kg/day once daily; maximum daily dose: 40 mg/day.
Erosive esophagitis associated with GERD:
Children 1 to 5 years: Limited data available: Oral: 0.3, 0.6, or 1.2 mg/kg/day once daily for 8 weeks was used in a dose-finding study of 60 patients with histologic or erosive esophagitis. High-dose treatment (1.2 mg/kg/day) was administered as a fixed dose of either: 15 mg for 1-year-olds or 20 mg for 2- to 5-year-olds. Patients with erosive esophagitis (n=4) received either 0.6 or 1.2 mg/kg/day. All patients had symptomatic improvement and patients with erosive esophagitis were healed by week 8; no dose response relationship was demonstrated (Baker 2010).
Children ≥5 years and Adolescents: Oral:
≥15 to <40 kg: 20 mg once daily for up to 8 weeks.
≥40 kg: 40 mg once daily for up to 8 weeks.
Gastric acid suppression; oral therapy not appropriate or tolerated: Limited data available; dosing regimens variable: Note: Dosing based on pharmacokinetic data from 39 pediatric patients (age range: 10 days to 16 years) which has shown doses within this range produce similar AUC as adult patients with comparable dosing; efficacy was not evaluated in either trial (Kearns 2008; Pettersen 2009). Parenteral therapy should be discontinued as soon as the patient tolerates oral therapy.
Weight-based dosing: Children ≥2 years and Adolescents: IV: 0.8 or 1.6 mg/kg once daily; maximum single dose: 80 mg; dosing from a single dose pharmacokinetic study in 18 patients (age range: 2 to 14 years) (Kearns 2008). In the BSA-based dosing trial (Pettersen 2009), the final median dose when standardized to weight was 1.1 mg/kg/day (range: 0.5 to 4.6 mg/kg/day). (Note: The 4.6 mg/kg/day dose was a prescription error; however, the patient experienced no adverse consequences due to high dose). Additionally, some clinicians have used 1 to 2 mg/kg/day in single or divided doses. Note: In a very small trial (n=8), a median dose of 1.1 mg/kg (0.9 to 2.5 mg/kg) produced similar AUC values as adults, but only produced a definable response (gastric pH >4) in one patient; in the remaining seven patients the mean percentage of time with intragastric pH ≥4 was 7.4 % (Pettersen 2005); the pharmacodynamic profile needs further defined (Pettersen 2009).
BSA-based dosing: Infants, Children, and Adolescents: IV: 40 mg/1.73 m2/day; if inadequate response (eg, continued symptoms or target gastric pH not achieved) may titrate up to a maximum dose of 80 mg/1.73 m2/day; dosing based on multidose pharmacokinetic analysis; in the final analysis, the median reported dose was 41.8 mg/1.73 m2/day (range: 19.9 to 140.6 mg/1.73 m2/day) (Note: The 140.6 mg/1.73 m2/day dose was a prescription error; however, the patient experienced no adverse consequences due to high dose) (Pettersen 2009).
Discontinuation of therapy: Oral: Based on experience in adults, some experts recommend a step-down approach in order to avoid worsening or rebound symptoms. One recommendation is to decrease the dose by 50% over 2 to 4 weeks. If the patient is already on the lowest possible dose, alternate day therapy may be considered. If symptoms worsen during treatment or after discontinuation, patient should be reevaluated (Kim 2018).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function: Children ≥5 years and Adolescents: Oral:
Mild to severe impairment: There are no pediatric-specific recommendations; based on experience in adult patients, no dosage adjustment necessary (Andersson 1996; Benet 1994).
Hemodialysis, intermittent: Poorly dialyzed (~2%): There are no pediatric-specific recommendations for dosing in patients receiving hemodialysis; based on experience in adult patients, no supplemental dose or dosage adjustment necessary (Kliem 1998).
There are no pediatric-specific recommendations; based on experience in adult patients, dosing adjustment suggested in some cases.
(For additional information see "Pantoprazole: Drug information")
Note: Do not administer concomitantly with other antisecretory agents, such as H2-receptor antagonists (H2RAs), prostaglandin analogues (eg, misoprostol), or somatostatin analogues (eg, octreotide), due to decreased acid-inhibitory effects; if another antisecretory agent is needed, allow a sufficient time interval between administration (ie, morning pantoprazole and bedtime H2RA) (ACG [Katz 2013]; Wolfe 2000; Wolfe 2020).
Aspiration prophylaxis in patients undergoing anesthesia (off-label use):
Note: May be considered in patients at high risk for aspiration (ASA 2017).
Oral: 40 mg given the night before surgery and 40 mg given the morning of surgery (Bhattacharyya 2011; Puig 2012).
IV: 40 mg as a single dose 1 hour prior to induction anesthesia (Brown 2019; Memiş 2003; Pisegna 2009; Puig 2012).
Barrett esophagus (off-label use):
Oral: 40 mg once daily; may increase the dose to 40 mg twice daily if needed to eliminate gastroesophageal reflux disease (GERD) symptoms or heal reflux esophagitis. Long-term maintenance therapy is recommended (ACG [Shaheen 2016]; Babic 2015; Spechler 2020).
Dyspepsia, functional (idiopathic or non-ulcer) (off-label use):
Note: For patients who test negative for Helicobacter pylori infection or have persistent symptoms following H. pylori eradication (ACG/CAG [Moayyedi 2017]; Longstreth 2020).
Oral: 20 to 40 mg once daily for a 4- to 8-week trial (Jung 2016; Pinto-Sanchez 2017; van Rensburg 2008); can be continued for a longer duration in patients with symptom improvement. Some experts recommend attempting to discontinue every 6 to 12 months to minimize the long-term risk of therapy (Longstreth 2020).
Eosinophilic esophagitis (off-label use):
Oral: 40 mg twice daily for an 8-week trial (Laserna-Mendieta 2020; Lucendo 2016; Vazquez-Elizondo 2013). Once 8-week trial is complete and remission is achieved, the dose may be gradually lowered to an individualized maintenance level (Laserna-Mendieta 2020). Some experts initiate with once-daily dosing and increase to twice-daily dosing after 4 weeks if symptoms fail to improve (Bonis 2021).
Gastroesophageal reflux disease, erosive or nonerosive:
Initial therapy:
Mild/intermittent disease (<2 episodes/week) and no evidence of erosive esophagitis:
Note: Some experts reserve proton pump inhibitors (PPIs) for patients who have residual acid reflux symptoms despite twice-daily H2RA (Kahrilas 2020).
Oral: 20 mg once daily, can increase to 40 mg once daily after 4 to 8 weeks if necessary. Discontinue once asymptomatic for 8 weeks (Kahrilas 2020).
Severe and/or frequent symptoms (≥2 episodes/week), and/or erosive esophagitis:
Oral: 40 mg once daily; once symptoms are controlled, continue for at least 8 weeks (Kahrilas 2020; Province of British Columbia Ministry of Health 2015; Wolfe 2000). Subsequently, patients without severe erosive esophagitis or Barrett esophagus can taper to the lowest dose necessary to control symptoms (and/or switch to an H2RA blocker), then discontinue acid suppression once asymptomatic. Patients with severe erosive esophagitis or Barrett esophagus should continue long-term maintenance therapy with 40 mg once daily (Kahrilas 2020; Ramakrishnan 2002; Spechler 2020).
IV (in patients unable to receive oral medications): 40 mg once daily, then switch to oral when possible (Metz 2000).
Residual symptoms despite 40 mg once daily therapy:
Note: Referral to a specialist is recommended.
Oral: Options include splitting the dose to 20 mg twice daily, increasing the dose to 40 mg twice daily, or switching to another PPI (ACG [Katz 2013]; Fass 2019; Wang 2009).
Helicobacter pylori eradication (off-label use):
Oral: 40 mg or 80 mg twice daily as part of an appropriate combination regimen with antibiotics. Dose depends on the selected regimen (ACG [Chey 2017]; Crowe 2020; Fallone 2016).
Nonsteroidal anti-inflammatory drugs (including aspirin)-induced ulcers, primary prevention (off-label use):
Note: For select patients at moderate or high risk for GI toxicity. These include patients with a history of GI ulcer, on dual antiplatelet therapy (eg, aspirin plus a P2Y12 inhibitor), on concurrent anticoagulant therapy, or with multiple additional risk factors (eg, corticosteroid use, high nonsteroidal anti-inflammatory drug [NSAID] dose, H. pylori infection) (Feldman 2021b; Holmes 2019). For patients on dual antiplatelet therapy, some experts reserve prophylaxis for those with additional risk factors (ACCF/ACG/AHA [Abraham 2010]; ESC [Ibanez 2018]). If present, H. pylori infection should be treated first (ACG [Lanza 2009]; Feldman 2021b).
Oral: 20 to 40 mg once daily for the duration of high-risk NSAID use (Bianchi Porro 2000; Cuisset 2009; Regula 2006; Sibbing 2009).
Peptic ulcer disease, treatment and secondary prevention (off-label use):
Note: For patients on NSAIDs (including aspirin), the NSAID should be discontinued, if possible (Feldman 2019a). If present, H. pylori infection should be treated first; uncomplicated H. pylori–associated ulcers may not need PPI treatment beyond that included in the eradication regimen (Vakil 2019).
Uncomplicated ulcer: Oral: 40 mg once daily. Duration depends on the size, location, and cause of ulcer and ranges from 4 to 8 weeks (Cremer 1995; Rehner 1995; Savarino 1998; Witzel 1995). In patients with refractory or recurrent disease, may increase the dose to 40 mg twice daily (Vakil 2019; Vakil 2020a).
Complicated ulcer (perforation, penetration, or gastric outlet obstruction): Oral, IV: 40 mg twice daily for 4 weeks, followed by 40 mg once daily. Duration depends on the location and etiology of ulcer (Vakil 2020b).
Bleeding ulcer:
Initial therapy: Note: Optimal pre-endoscopic PPI therapy is uncertain. Some experts suggest initiating high-dose IV PPI with continuous or intermittent dosing in patients with suspected active upper GI bleed prior to endoscopy (Saltzman 2020). Following endoscopy, for patients with high-risk stigmata of recent bleeding (eg, active bleed, visible vessel, adherent clot), a continuous infusion of an IV PPI for at least 72 hours before transitioning to an oral PPI is recommended (ACG [Laine 2021]; Barkun 2019). Patients without high-risk stigmata of recent bleeding can be switched to an oral PPI immediately after endoscopy (Saltzman 2020).
IV: Continuous infusion: Loading dose of 80 mg, followed by 8 mg/hour continuous infusion for a total of 72 hours (ACG [Laine 2021]; Barkun 2019; Sung 2010; van Rensburg 2009; Zargar 2006).
IV: Intermittent dosing: Loading dose of 80 mg, followed by 40 mg every 12 hours (ACG [Laine 2021]; Hsu 2010; Hung 2007; Yamada 2012).
Oral:
Patients with high-risk stigmata of recent bleeding on endoscopy (following IV PPI therapy): 40 mg twice daily for 14 days, followed by 40 mg once daily (Barkun 2019; Saltzman 2020).
Patients with no high-risk stigmata of recent bleeding on endoscopy: 20 mg once daily (Saltzman 2020).
Duration: The total duration of treatment depends on size, location, and cause of the ulcer and ranges from 4 to 12 weeks (Barkun 2019; Saltzman 2020; Vakil 2019; Vakil 2020a).
Maintenance therapy/secondary prevention: Note: For select high-risk patients (eg, idiopathic ulcers, frequently recurrent ulcers, need for continued NSAID use).
Oral: 20 to 40 mg once daily (Feldman 2019a; Ng 2010; Sung 2010).
Stress ulcer prophylaxis in select critically ill patients (off-label use):
Note: For ICU patients with associated risk factors for GI bleeding (including coagulopathy, mechanical ventilation for >48 hours, traumatic brain injury, history of GI ulceration or bleeding within past year, extensive burns) (Rhodes 2017; Weinhouse 2019).
IV: 40 mg once daily (Alhazzani 2017; Krag 2018; Selvanderan 2016).
Oral or via nasogastric tube: 40 mg once daily (Spirt 2006; Wensel 2009).
Duration: Discontinue prophylaxis once critical illness and modifiable risk factors have resolved (Rhodes 2017; Weinhouse 2019).
Zollinger-Ellison syndrome:
Oral: Initial: 80 mg twice daily; if needed, may titrate upward early in therapy to a maximum of 240 mg/day (as either 80 mg three times daily or 120 mg twice daily); once acid output has been controlled, gradual dose reductions are usually possible; reported maintenance dosage range: 40 to 200 mg/day (mean: 116 mg/day); daily doses ≥80 mg are usually given in 2 to 3 divided doses; continue therapy as long as clinically indicated (Bergsland 2020; Metz 2006; Ramdani 2002).
IV (when oral administration is not possible): Initial: 80 mg every 8 to 12 hours; doses up to 240 mg/day (given as 120 mg every 12 hours or 80 mg every 8 hours) have been used for a limited period of time (up to 6 days); switch to oral administration when possible (Lew 2000; Metz 2001).
Discontinuation of therapy: In patients who have received continuous therapy for >6 months, some experts gradually taper therapy until discontinuation to avoid worsening or rebound symptoms. There is no single agreed upon discontinuation strategy. If the patient is receiving 40 mg once or twice daily, some experts decrease the dose by 50% every week. For patients receiving twice-daily dosing, the first dose reduction can be achieved by decreasing to once-daily AM dosing. Once patients are on the lowest dose for 1 week, discontinue therapy (Wolfe 2020). An alternative strategy is to decrease the dose by 50% over 2 to 4 weeks, then discontinue. If the patient is already on the lowest possible dose, alternate-day therapy may be considered (Kim 2018). In addition, as-needed therapy with an H2RA or an antacid can be used during the taper (Haastrup 2014).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
IV, Oral:
Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (Andersson 1996; Benet 1994).
Hemodialysis, intermittent (thrice weekly): Poorly dialyzed (~2%): No supplemental dose or dosage adjustment necessary (Kliem 1998).
Peritoneal dialysis: No dosage adjustment necessary (expert opinion).
CRRT: No dosage adjustment necessary (expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (expert opinion).
No dosage adjustment necessary; doses >40 mg daily have not been evaluated.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Packet, Oral:
Protonix: 40 mg (1 ea, 30 ea) [contains polysorbate 80]
Generic: 40 mg (1 ea, 30 ea)
Solution Reconstituted, Intravenous:
Generic: 40 mg (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Protonix: 40 mg (1 ea) [contains edetate (edta) disodium]
Generic: 40 mg (1 ea)
Tablet Delayed Release, Oral:
Protonix: 20 mg, 40 mg
Generic: 20 mg, 40 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Generic: 40 mg (1 ea)
Tablet Delayed Release, Oral:
Pantoloc: 20 mg, 40 mg [contains polysorbate 80]
Tecta: 40 mg
Generic: 20 mg, 40 mg
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Protonix granules for oral suspension, delayed release tablets: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020987s056,022020s018lbl.pdf#page=33
Parenteral: IV: Not for IM or SubQ use. Flush IV line with NS, D5W, or LR before and after administration.
IV push: Administer over 2 minutes at a concentration of 4 mg/mL.
Intermittent IV infusion: Using a 0.4 to 0.8 mg/mL solution, infuse over 15 minutes at a rate not to exceed 7 mL/minute.
Oral:
Tablet: Should be swallowed whole; do not chew or crush. May be taken without regard to meals; however, best if taken 30 minutes before a meal (AAP [Lightdale 2013]); may be administered with antacids.
Delayed-release oral suspension: Should only be administered in apple juice or applesauce and administered 30 minutes before a meal; do not chew or crush granules. Do not administer in water, other liquids, or foods. Per manufacturer's labeling, do not divide the 40 mg delayed-release oral suspension packet to create a 20 mg dosage for pediatric patients who are unable to take the tablet formulation.
Oral administration in apple juice: Empty intact granules into 5 mL of apple juice, stir for 5 seconds (granules will not dissolve), and swallow immediately. Rinse container once or twice with apple juice and swallow immediately.
Oral administration in applesauce: Sprinkle intact granules on 1 teaspoonful of applesauce; swallow within 10 minutes of preparation. Sips of water should be administered to ensure granules are washed down into stomach; repeat sips as needed.
Nasogastric tube administration: Separate the plunger from the barrel of a 60 mL catheter tip syringe and connect to a ≥16 French nasogastric tube. Holding the syringe attached to the tubing as high as possible, empty granules into barrel of syringe, add 10 mL of apple juice, and gently tap/shake the barrel of the syringe to help empty the syringe. Add an additional 10 mL of apple juice and gently tap/shake the barrel to help rinse. Repeat rinse at least twice more with 10 mL aliquots of apple juice. No granules should remain in the syringe.
Oral administration in syringe: In neonatal trials, fixed dosage packets of 2.5 mg pantoprazole were mixed with grape flavoring and 2.5 mL of water and administered immediately (Ward 2010).
IV: Flush IV line before and after administration with D5W, NS, or LR. In-line filter not required.
2-minute infusion: The volume of reconstituted solution (4 mg/mL) may be administered IV over at least 2 minutes.
15-minute infusion: Infuse over ~15 minutes at a rate of ~7 mL/minute.
Continuous infusion: May also be administered as a continuous infusion for the prevention of rebleeding with in peptic ulcer bleed (off-label use).
Oral:
Tablet: Should be swallowed whole, do not split, crush, or chew. For most indications, administer 30 to 60 minutes before a meal (preferably); best if taken before breakfast (ACG [Katz 2013]). If administering twice daily, first dose should be administered before breakfast and the second dose before dinner (ACG [Katz 2013]; Hershcovici 2010). Manufacturer’s labeling states that tablets may be administered with or without food and concomitant administration of antacids do not affect absorption.
Delayed-release oral suspension: Should only be administered in apple juice or applesauce and taken ~30 minutes before a meal; do not chew or crush granules. Do not administer with any other liquid (eg, water) or foods.
Oral administration in applesauce: Sprinkle intact granules on 1 teaspoon of applesauce and swallow within 10 minutes of preparation.
Oral administration in apple juice: Empty intact granules into 5 mL of apple juice, stir for 5 seconds (granules will not dissolve), and swallow immediately after preparation. Rinse container once or twice with apple juice and swallow immediately.
Nasogastric tube administration: Separate the plunger from the barrel of a 60 mL catheter tip syringe and connect to a ≥16 French nasogastric tube. Holding the syringe attached to the tubing as high as possible, empty the contents of the packet into barrel of the syringe, add 10 mL of apple juice and gently tap/shake the barrel of the syringe to help empty the syringe. Add an additional 10 mL of apple juice and gently tap/shake the barrel to help rinse. Repeat rinse at least twice with 10 mL aliquots of apple juice. No granules should remain in the syringe.
Bariatric surgery: Tablet, delayed release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Delayed-release tablet should be swallowed whole. Do not chew or crush. Oral suspension formulation is available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, for patients with refractory acid reflux, esophagitis, Barrett's esophagus, or ulcer, consider switching to an alternative proton pump inhibitor that is orally disintegrating (ie, lansoprazole Solutab) or a capsule formulation where contents of the capsule may be opened and taken with food (omeprazole, esomeprazole, lansoprazole). If there is inadequate response, consider escalation of therapy to twice a day or conversion to omeprazole/sodium bicarbonate or dexlansoprazole.
Oral: Store tablet and oral suspension at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
IV: Prior to reconstitution, store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not freeze. Protect from light prior to reconstitution; upon reconstitution, protection from light is not required. Do not freeze reconstituted solution. Per manufacturer's labeling, reconstituted solution is stable at room temperature for up to 6 hours; further diluted (admixed) solution in D5W, LR, or NS should be stored at room temperature and used within 24 hours from the time of initial reconstitution. However, studies have shown that reconstituted solution (4 mg/mL) in polypropylene syringes is stable up to 96 hours at room temperature (Johnson 2005). Upon further dilution, the admixed solution should be used within 96 hours from the time of initial reconstitution. The preparation should be stored at 3°C to 5°C (37°F to 41°F) if it is stored beyond 48 hours to minimize discoloration.
Oral: Short-term treatment (up to 8 weeks) of erosive esophagitis associated with gastroesophageal reflux disease (GERD) (FDA approved in ages ≥5 years and adults); maintenance of healing of erosive esophagitis (FDA approved in adults); treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome (FDA approved in adults); has also been used as adjunctive therapy of duodenal ulcers associated with Helicobacter pylori.
IV: Short-term treatment (7 to 10 days) of GERD with a history of erosive esophagitis (FDA approved in adults); treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome (FDA approved in adults); has also been used as an alternative to oral therapy in patients who are unable to continue taking oral pantoprazole.
Pantoprazole may be confused with ARIPiprazole
Protonix may be confused with Lotronex, Lovenox, protamine
Vials containing Protonix IV for injection are not recommended for use with spiked IV system adaptors. Nurses and pharmacists have reported breakage of the glass vials during attempts to connect spiked IV system adaptors, which may potentially result in injury to healthcare professionals.
Beers Criteria: Proton pump inhibitors are identified in the Beers Criteria as potentially inappropriate medications to be avoided (as scheduled use for more than 8 weeks) in patients 65 years and older due to their risk of C. difficile infection and bone loss/fractures unless given for high-risk patients (eg, oral corticosteroid or chronic NSAID use), patients with erosive esophagitis, Barrett's esophagitis, a pathological hypersecretory condition, or if the patient has demonstrated a need for maintenance therapy (eg, failure of drug discontinuation trial or failure of H2 blockers) (Beers Criteria [AGS 2019]).
Protonix [US] may be confused with Pretanix brand name for indapamide [Hungary]
Protonix: Brand name for pantoprazole [US] but also the brand name for omeprazole [Philippines]
Cutaneous lupus erythematosus, most often subacute cutaneous lupus erythematosus (SCLE), has been reported with use of proton pump inhibitors (PPIs), including pantoprazole (Ref). SCLE is reversible (resolution ~3 months following discontinuation [range: 4 weeks to 8 months]), and cross-reactivity between PPIs has been reported (Ref). SCLE may present as a widespread skin rash which may include bullous lesions and focal skin necrosis (Ref). In addition, systemic lupus erythematosus (SLE) secondary to PPIs may occur, although less often as compared to SCLE. Presentation often includes rash, however, arthralgia or cytopenia may also occur.
Mechanism: Non-dose-related; immunologic. SCLE is typically associated with positive antinuclear antibodies (ANA), anti-Ro/SSA and anti-La/SSB antibodies (Ref).
Onset: Varied.
Cutaneous lupus erythematosus: ~8 months following treatment initiation (range: 3 days to 3.5 years) (Ref).
Systemic lupus erythematosus: According to the manufacturer, may occur within days to years after initiating treatment.
Risk factors:
• Prior history or family history of SCLE, especially secondary to PPIs (Ref)
• Presence of risk factors for SCLE (eg, female of childbearing age, periods of female hormone changes, prior history of drug allergies, sun-reactive skin, exposure to UV radiation) (Ref)
Use of proton pump inhibitors (PPIs), including pantoprazole, may increase risk of enteric infections, including gastroenteritis and Clostridioides difficile associated diarrhea (CDAD) in adults and pediatric patients (Ref); however, data are conflicting, especially with regards to CDAD (Ref). Diarrhea, which may be a result of enteric infection, is the most common adverse reaction secondary to long-term PPI use and often results in treatment discontinuation (Ref). Consider CDAD diagnosis in patients with persistent diarrhea that does not improve, especially in hospitalized patients.
Mechanism: Dose-related (Ref); related to the pharmacologic action. The increase in gastric pH secondary to PPI administration leads to changes in intestinal microbial environment which may allow for intestinal germination and growth of C. difficile spores as well as colonization by other bacteria responsible for enteric infections (eg, Salmonella, Campylobacter, Shigella, norovirus) (Ref).
Onset: Varied; hospitalized patients receiving high doses may experience CDAD within days of treatment initiation (Ref); whereas, others develop gastroenteritis with long-term therapy in the community setting (Ref).
Risk factors:
• High doses of PPIs (eg, daily or more frequently than daily use) (Ref)
• Hospitalized patients (Ref)
• Infants and children with defective immune systems or indwelling catheters (Ref)
Use of proton pump inhibitors (PPIs), including pantoprazole, may increase the risk of bone fracture in children, young adults, and older adults, including osteoporosis-related fractures (Ref). However, data regarding the impact of PPIs on fractures, as well as bone mineral density (BMD), are inconclusive and some have concluded that any association with fracture may be related to other independent risk factors (Ref).
Mechanism: Dose-related; related to the pharmacologic action (ie, hypergastrinemia and hypochlorhydria). Hypergastrinemia causes secondary hyperparathyroidism which can increase bone resorption and subsequent decreased bone mineral density. Hypochlorhydria results in decreased absorption of calcium, magnesium, and vitamin B12. Impaired calcium absorption may cause secondary hyperparathyroidism and decreased BMD. Decreased vitamin B12 absorption may decrease osteoblastic activity leading to decreased BMD, as well as decreased collagen cross-linking leading to weakened bone structure (Ref).
Onset: Delayed (≥1 year) (Ref).
Risk factors:
• Presence of risk factors for fractures and/or osteoporosis (Ref)
• Duration of therapy (eg, ≥1 year) (Ref)
• High doses of PPIs (eg, ≥1.5 doses per day) (Ref)
Long-term use of proton pump inhibitors (PPIs) has been associated with the development of reversible gastric polyp (fundic gland) (Ref). Most PPI users who developed fundic gland polyps were asymptomatic. Symptomatic patients may report nausea, vomiting, or abdominal pain. GI bleeding and/or anemia may occur with ulcerated polyp. Clinicians should note that Helicobacter pylori infection may be protective against fundic gland polyps as bacterial proteases help glandular outflow by breaking down blockages (Ref).
Mechanism: Time-related; long-term use of PPIs is associated with an increase in the prevalence of parietal cell protrusions which cause outflow blockage of the isthmus and subsequent formation of fundic gland cysts. As therapy continues, fundic gland cysts may enlarge and develop into fundic gland polyps (Ref).
Onset: Delayed (>1 year) (Ref)
Risk factors:
• Patients with familial adenomatous polyposis (Ref)
• Duration of treatment (>1 year and especially ≥5 years) (Ref)
Immediate hypersensitivity reactions secondary to proton pump inhibitors (PPIs) range from urticaria to rare cases of anaphylaxis (Ref). Delayed hypersensitivity reactions include maculopapular rash (Ref) as well as rare severe cutaneous adverse reactions (SCARs) such as acute generalized exanthematous pustulosis (Ref), drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis (Ref). IV pantoprazole has also been associated with skin rash and pruritus.
Mechanism: Non-dose-related; immunologic.
Immediate hypersensitivity reactions (eg, anaphylaxis, urticaria): IgE-mediated (Ref).
Delayed hypersensitivity reactions (including maculopapular rash and SCARs): T-cell-mediated (Ref).
Onset:
Immediate hypersensitivity reactions: Rapid; occurs within 1 hour of administration but may occur up to 6 hours after exposure (Ref).
Delayed hypersensitivity reactions:
Maculopapular reactions: Intermediate; generally occurs 7 to 10 days after initiation, but may occur up to 1 month following initiation of therapy (Ref).
Other reactions (including SCARs): Varied; occurs after 7 to 14 days up to 3 months following initiation of therapy (Ref).
Risk factors:
• Prior history of hypersensitivity reaction to PPIs (Ref)
• Cross-reactivity has been noted with PPIs; although, cross-reactivity patterns have been variable (Ref)
Long-term use of proton pump inhibitors (PPIs), including pantoprazole, has resulted in reversible hypomagnesemia (Ref). Symptoms may be severe (eg, tetany, cardiac arrhythmias, cerebellar syndrome, seizures) and resistant to treatment with supplementation (Ref). May require discontinuation of PPI in addition to magnesium supplementation in ~25% of patients. Following discontinuation, magnesium normalizes after ~1 week (Ref). Hypomagnesemia may recur if PPI therapy is restarted (Ref).
Mechanism: Time-related; the specific mechanism is unknown; however, long-term use of PPIs may be associated with changes in intestinal absorption of magnesium (Ref).
Onset: Delayed; hypomagnesemia occurs most often after 1 year of therapy but may occur as early as 3 months (Ref). In patients with prior PPI-induced hypomagnesemia, re-initiation may result in recurrence within 2 weeks (Ref).
Risk factors:
• Duration of therapy (≥3 months and especially >1 year) (Ref)
• Concurrent use of other drugs that cause hypomagnesemia (eg, digoxin, loop diuretics, thiazide diuretics) (Ref)
• Patients who have undergone kidney transplantation (Ref)
Acute interstitial nephritis (AIN) may occur rarely (Ref), with renal biopsy showing diffuse interstitial infiltrate and tubulitis (Ref). Patients generally achieve complete or partial recovery by 6 months following treatment for AIN (Ref). Signs of systemic hypersensitivity (fever, rash, eosinophilia) often seen in other cases of drug-induced AIN are not typically observed in proton pump inhibitor (PPI)-induced AIN (Ref). Clinicians should note that there appears to be no correlation between duration of exposure to PPI and duration or severity of acute renal failure after resolution of AIN (Ref).
Mechanism: Non-dose-related; unknown, although may be immunologic (Ref).
Onset: Varied; usually occurs within 3 months (Ref). Upon reexposure symptoms often present more rapidly, often within 12 hours (Ref).
Risk factors:
• Older adults; although this may be due to increased use of PPIs (Ref)
• Cross-reactions among PPIs in patients who developed AIN is not known
Long-term use of acid suppressive therapies, including pantoprazole, may result in reversible vitamin B12 deficiency; however, data regarding the clinical significance of these changes and causality are conflicted (Ref).
Mechanism: Dose- and time-related; acid suppressive therapies interfere with acid-activated proteolytic digestion of dietary protein-bound vitamin B12 in the stomach, thereby resulting in malabsorption of vitamin B12 (Ref).
Onset: Delayed
Risk factors:
• Duration of therapy (≥2 to 3 years); the association between ≥2 years of PPI use and vitamin B12 deficiency was stronger among people <30 years of age and in females (Ref)
• High doses of PPIs (≥1.5 pills per day (Ref))
• Presence of risk factors for vitamin B12 deficiency (eg, malnourished patients, vegan diet) (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidences are associated with adults unless otherwise specified.
>10%: Nervous system: Headache (adults: 12%; children and adolescents: >4%)
1% to 10%:
Cardiovascular: Edema (≤2%), facial edema (children, adolescents, and adults: ≤4%), thrombophlebitis (IV: ≤2%)
Dermatologic: Pruritus (≤2%), skin photosensitivity (≤2%), skin rash (children and adolescents: >4%; adults: ≤2%), urticaria (children, adolescents, and adults: ≤4%)
Endocrine & metabolic: Increased serum triglycerides (children, adolescents, and adults: ≤4%)
Gastrointestinal: Abdominal pain (children and adolescents: >4%), constipation (children, adolescents, and adults: ≤4%), diarrhea (children, adolescents, and adults: 4% to 9% [placebo: 5%]), flatulence (children and adolescents: ≤4%), nausea (children and adolescents: ≤4%), vomiting (children, adolescents, and adults: ≥4%), xerostomia (≤2%)
Hematologic & oncologic: Leukopenia (≤2%), thrombocytopenia (≤2%)
Hepatic: Hepatitis (≤2%), increased liver enzymes (children, adolescents, and adults: ≤4%)
Hypersensitivity: Hypersensitivity reaction (children, adolescents, and adults: ≤4%)
Nervous system: Depression (≤2%), dizziness (children, adolescents, and adults: ≤4%), vertigo (children, adolescents, and adults: ≤4%)
Neuromuscular & skeletal: Arthralgia (children, adolescents, and adults: ≤4%), increased creatine phosphokinase in blood specimen (children, adolescents, and adults: ≤4%), myalgia (children, adolescents, and adults: ≤4%)
Ophthalmic: Blurred vision (≤2%)
Respiratory: Upper respiratory tract infection (children and adolescents: >4%)
Miscellaneous: Fever (children and adolescents: >4%; adults: ≤2%)
Frequency not defined: Miscellaneous: Laboratory test abnormality (false-positive for THC)
Postmarketing:
Cardiovascular: Acute coronary syndrome (Canpolat 2012)
Dermatologic: Acute generalized exanthematous pustulosis (rare: <1%), cutaneous lupus erythematosus (subacute) (Almebayadh 2013, Correia 2001), maculopapular rash (rare: <1%) (Lin 2018), Stevens-Johnson syndrome (rare: <1%) (Lin 2018), toxic epidermal necrolysis (rare: <1%) (Lin 2018)
Endocrine & metabolic: Hypomagnesemia (rare: <1%) (Bhana 2017, Hoorn 2010), hyponatremia (Ferreira 2016), vitamin B12 deficiency (Lam 2013), weight changes
Gastrointestinal: Ageusia, Clostridioides difficile associated diarrhea (rare: <1%), dysgeusia, gastric polyp (fundic gland; with chronic use [>1 year]: common: ≥10%) (Jalving 2006), gastroenteritis (rare: <1%) (Howell 2010), pancreatitis (Das 2012)
Hematologic & oncologic: Agranulocytosis, neutropenia (Gouraud 2010), pancytopenia, thrombocytopenia (Kallam 2015; Watson 2006)
Hepatic: Hepatic failure (Yusoff 1999), hepatotoxicity (Aslan 2014, Meunier 2018, Sandig 2011)
Hypersensitivity: Anaphylaxis (rare: <1%) (Fardet 2002, Faridaalaee 2018; Gupta 2018, Lai 2011), angioedema (Bose 2013)
Immunologic: Drug reaction with eosinophilia and systemic symptoms (rare: <1%) (Schmitz 2018)
Nervous system: Confusion, dementia (Gomm 2016), drowsiness, fatigue, hallucination, insomnia
Neuromuscular & skeletal: Asthenia, bone fracture (Nassar 2018), rhabdomyolysis (Yusoff 1999)
Renal: Acute interstitial nephritis (rare: <1%) (Klassen 2013), renal disease (chronic; Lazarus 2016)
Respiratory: Pneumonia (adults and pediatric patients 4 to 36 months of age) (Canani 2006, Eom 2011)
Hypersensitivity (eg, anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, urticaria) to pantoprazole, other substituted benzimidazole proton pump inhibitors, or any component of the formulation; in combination with rilpivirine-containing products.
Canadian labeling: Additional contraindications (not in US labeling): Concomitant use with rilpivirine
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 regard to tumorigenicity in humans is not known.
• Hepatic effects: Dosage adjustments are not required with hepatic dysfunction.
Disease-related concerns:
• Gastric malignancy: Relief of symptoms does not preclude the presence of a gastric malignancy.
Concurrent drug therapy issues:
• Clopidogrel: 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).
Dosage form specific issues:
• Edetate sodium (EDTA): Some dosage forms may contain 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 2017).
• Laboratory test interference: Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acid; may cause false-positive results in diagnostic investigations for neuroendocrine tumors. Temporarily stop pantoprazole treatment at least 14 days before CgA test; if CgA level is high, repeat test to confirm. Use same commercial laboratory for testing to prevent variable results.
Substrate of CYP2C19 (minor), CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Acalabrutinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Acalabrutinib. Risk X: Avoid combination
Amphetamine: Inhibitors of the Proton Pump (PPIs and PCABs) may increase the absorption of Amphetamine. Risk C: Monitor therapy
Atazanavir: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Atazanavir. Management: Avoid use in treatment-experienced patients. In treatment-naive patients, administer boosted atazanavir 12 hours after the PPI and the PPI dose should not exceed the equivalent of 20 mg omeprazole. Monitor for reduced atazanavir efficacy. Risk D: Consider therapy modification
Belumosudil: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Belumosudil. Management: Increase the dose of belumosudil to 200 mg twice daily when coadministered with proton pump inhibitors. Risk D: Consider therapy modification
Bisphosphonate Derivatives: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Bosutinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Bosutinib. Management: Consider alternatives to proton pump inhibitors and potassium-competitive acid blockers, such as short-acting antacids or histamine-2 receptor antagonists. Administer alternative agents more than 2 hours before or after bosutinib. Risk D: Consider therapy modification
Capecitabine: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Capecitabine. Risk C: Monitor therapy
Cefditoren: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Cefditoren. Management: If possible, avoid use of cefditoren with proton pump inhibitors (PPIs) and potassium-competitive acid blockers (PCABs). Consider alternative methods to control acid reflux or use alternative antimicrobial therapy if coadministration is required. Risk D: Consider therapy modification
Cefpodoxime: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Cefpodoxime. Risk C: Monitor therapy
Cefuroxime: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the absorption of Cefuroxime. Risk X: Avoid combination
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 C: Monitor therapy
Cysteamine (Systemic): Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Cysteamine (Systemic). Risk C: Monitor therapy
Dacomitinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Dacomitinib. Management: Avoid concurrent use of dacomitinib with PPIs and PCABs. Antacids may be used. Histamine H2-receptor antagonists (HR2A) may be used if dacomitinib is given at least 6 hours before or 10 hours after the H2RA. Risk X: Avoid combination
Dasatinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Dasatinib. Management: Antacids (taken 2 hours before or after dasatinib administration) can be used in place of PPIs or PCABs if some acid-reducing therapy is needed. Risk X: Avoid combination
Delavirdine: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Delavirdine. Management: Chronic therapy with PPIs or PCABs should be avoided in patients treated with delavirdine. The clinical significance of short-term PPI or PCAB therapy with delavirdine is uncertain, but such therapy should be undertaken with caution. Risk X: Avoid combination
Dextroamphetamine: Inhibitors of the Proton Pump (PPIs and PCABs) 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
Doxycycline: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the bioavailability of Doxycycline. Risk C: Monitor therapy
Enoxacin: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the absorption of Enoxacin. Risk C: Monitor therapy
Erlotinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Erlotinib. Risk X: Avoid combination
Gefitinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Gefitinib. Management: Avoid use of inhibitors of the proton pump (PPIs or PCABs) with gefitinib when possible. If required, administer gefitinib 12 hours after the PPI/PCAB or 12 hours before the next dose of the PPI/PCAB. Closely monitor clinical response to gefitinib. Risk D: Consider therapy modification
Immune Checkpoint Inhibitors: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Indinavir: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Indinavir. Risk C: Monitor therapy
Infigratinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease serum concentrations of the active metabolite(s) of Infigratinib. Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Infigratinib. Risk X: Avoid combination
Itraconazole: Inhibitors of the Proton Pump (PPIs and PCABs) may increase the serum concentration of Itraconazole. Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Itraconazole. Management: Exposure to Tolsura brand itraconazole may be increased by PPIs or PCABs ; consider itraconazole dose reduction. Exposure to Sporanox brand itraconazole may be decreased. Give Sporanox brand itraconazole at least 2 hrs before or 2 hrs after PPIs or PCABs. Risk D: Consider therapy modification
Ketoconazole (Systemic): Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the absorption of Ketoconazole (Systemic). Ketoconazole (Systemic) may increase the serum concentration of Inhibitors of the Proton Pump (PPIs and PCABs). Management: Administer ketoconazole with an acidic beverage, such as non-diet cola, to increase gastric acidity and improve absorption if concomitant use with proton pump inhibitors or potassium-competitive acid blockers is necessary. Risk D: Consider therapy modification
Ledipasvir: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Ledipasvir. Management: PPI or PCAB doses equivalent to omeprazole 20 mg or lower may be given with ledipasvir under fasted conditions. Use of ledipasvir with higher doses or with food, or 2 hours after a these agents, may reduce ledipasvir bioavailability. Risk D: Consider therapy modification
Levoketoconazole: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the absorption of Levoketoconazole. Levoketoconazole may increase the serum concentration of Inhibitors of the Proton Pump (PPIs and PCABs). Risk X: Avoid combination
Lumacaftor and Ivacaftor: May decrease the serum concentration of Inhibitors of the Proton Pump (PPIs and PCABs). Risk C: Monitor therapy
Methotrexate: Inhibitors of the Proton Pump (PPIs and PCABs) may increase the serum concentration of Methotrexate. Management: Consider temporarily interrupting PPI or PCAB therapy in patients receiving high-dose methotrexate. If coadministered, monitor for increased methotrexate toxicity (eg, mucositis, myalgias) and/or delayed methotrexate elimination. Risk D: Consider therapy modification
Multivitamins/Minerals (with ADEK, Folate, Iron): Inhibitors of the Proton Pump (PPIs and PCABs) 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: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Mycophenolate. Specifically, concentrations of the active mycophenolic acid may be reduced. Risk C: Monitor therapy
Nelfinavir: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease serum concentrations of the active metabolite(s) of Nelfinavir. Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Nelfinavir. Management: Due to potentially significant reductions in nelfinavir exposure, avoid concurrent use of nelfinavir with a PPI or PCAB when possible. If unavoidable, consider PPI or PCAB use for a short duration (less than 30 days) and closely monitor viral load. Risk D: Consider therapy modification
Neratinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Neratinib. Specifically, proton pump inhibitors may reduce neratinib absorption. Risk X: Avoid combination
Nilotinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Nilotinib. Management: Avoid this combination. Histamine H2 receptor antagonists (H2RAs) given 10 hours before or 2 hours after nilotinib, or antacids given 2 hours before or 2 hours after nilotinib are acceptable alternatives. Risk D: Consider therapy modification
Octreotide: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Octreotide. Risk C: Monitor therapy
Palbociclib: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Palbociclib. Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Palbociclib. Management: Carefully evaluate potential risks and benefits of coadministration of palbociclib and proton pump inhibitors or potassium-competitive acid blockers due to the risk of reduced palbociclib efficacy. Palbociclib capsules should be taken with food. Risk D: Consider therapy modification
PAZOPanib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of PAZOPanib. Risk X: Avoid combination
Pexidartinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Pexidartinib. Management: Avoid this combination. If acid-reduction is needed, consider administering an antacid 2 hours before or after pexidartinib, or administer pexidartinib 2 hours before or 10 hours after an H2 receptor antagonist. Risk X: Avoid combination
Posaconazole: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Posaconazole. Management: Avoid coadministration of PPIs or PCABs and posaconazole oral suspension. Posaconazole delayed-release tablets do not appear to be sensitive to this interaction and do not required dose adjustment if coadministered with PPIs or PCABs. Risk D: Consider therapy modification
Rilpivirine: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Riociguat: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Riociguat. Risk C: Monitor therapy
Risedronate: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the therapeutic effect of Risedronate. Inhibitors of the Proton Pump (PPIs and PCABs) may increase the serum concentration of Risedronate. This applies specifically to use of delayed-release risedronate. Management: Coadministration of PPIs or PCABs with delayed-release risedronate formulations is not recommended. Limit PPI/PCAB dose and duration during coadministration with risedronate as possible. Patients over age 70 are at higher risk of adverse effects. Risk D: Consider therapy modification
Saquinavir: Inhibitors of the Proton Pump (PPIs and PCABs) may increase the serum concentration of Saquinavir. Risk C: Monitor therapy
Secretin: Inhibitors of the Proton Pump (PPIs and PCABs) may diminish the diagnostic effect of Secretin. Specifically, use of PPIs may cause a hyperresponse in gastrin secretion in response to secretin stimulation testing, falsely suggesting gastrinoma. Management: Avoid concomitant use of PPIs or PCABs and secretin, and discontinue PPIs several weeks prior to secretin administration, with the duration of separation determined by the specific PPI. See full monograph for details. Risk D: Consider therapy modification
Selpercatinib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Selpercatinib. Management: Coadministration of selpercatinib and PPIs or PCABs should be avoided. If coadministration cannot be avoided, selpercatinib and PPIs or PCABs should be administered simultaneously with food. Risk D: Consider therapy modification
SORAfenib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the absorption of SORAfenib. Risk C: Monitor therapy
Sotorasib: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Sotorasib. Risk X: Avoid combination
Tipranavir: May decrease the serum concentration of Inhibitors of the Proton Pump (PPIs and PCABs). These data are derived from studies with Ritonavir-boosted Tipranavir. Risk C: Monitor therapy
Velpatasvir: Inhibitors of the Proton Pump (PPIs and PCABs) may decrease the serum concentration of Velpatasvir. Management: Sofosbuvir/velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Sofosbuvir/velpatasvir/voxilaprevir can be administered with omeprazole 20 mg. Use with other PPIs or PCABs has not been studied. Risk D: Consider therapy modification
Voriconazole: May increase the serum concentration of Inhibitors of the Proton Pump (PPIs and PCABs). Inhibitors of the Proton Pump (PPIs and PCABs) may increase the serum concentration of Voriconazole. Risk C: Monitor therapy
Prolonged treatment (≥2 years) may lead to malabsorption of dietary vitamin B12 and subsequent vitamin B12 deficiency (Lam, 2013).
IV: Due to EDTA in preparation, zinc supplementation may be needed in patients prone to zinc deficiency.
Recommendations for the treatment of gastroesophageal reflux disease in pregnancy are available. As in nonpregnant patients, lifestyle modifications followed by other medications are the initial treatments (Body 2016; Huerta-Iga 2016; Katz 2013; van der Woude 2014). Based on available data, PPIs may be used when clinically indicated (Body 2016; Matok 2012; Pasternak 2010; van der Woude 2014).
Proton pump inhibitor, suppresses gastric acid secretion by inhibiting the parietal cell H+/K+ ATP pump
Onset of action: Acid secretion: Oral: 2.5 hours; IV: 15 to 30 minutes.
Maximum effect: IV: 2 hours.
Absorption: Rapid, well absorbed.
Duration: Oral, IV: 24 hours.
Distribution: Vd:
Children and Adolescents (Kearns 2008): IV (2 to 16 years of age): 0.22 ± 0.14 L/kg; Oral (5 to 16 years of age): 0.24 ± 0.09 L/kg.
Adults: 11 to 23.6 L.
Protein binding: 98%, primarily to albumin.
Metabolism: Extensively hepatic; CYP2C19 (demethylation), CYP3A4; no evidence that metabolites have pharmacologic activity.
Bioavailability: ~77%.
Half-life elimination:
Neonates (PMA: 37 to 44 weeks): ~3 hours (Ward 2010).
Children and Adolescents (Kearns 2008): IV (2 to 16 years of age): 1.22 ± 0.68 hours; Oral (5 to 16 years of age): 1.27 ± 1.29 hours.
Adults: 1 hour; increased to 3.5 to 10 hours with CYP2C19 deficiency.
Time to peak:
Children and Adolescents (Kearns 2008): IV (2 to 16 years of age): 0.34 ± 0.12 hours; Oral (5 to 16 years of age): 2.54 ± 0.72 hours.
Adults: Oral: 2.5 hours.
Excretion: Urine (71% as metabolites); feces (18%); pantoprazole clearance increased with weight and age (Pettersen 2009).
Hepatic function impairment: Increase in serum elimination half-life to 7 to 9 hours; AUC increases by 5- to 7-fold.
Pediatric: 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.
Geriatric: Moderate increase in AUC (43%) and Cmax (26%) after oral administration.
Gender: A modest increase in AUC and Cmax in women.
2 mg/mL Oral Suspension
A 2 mg/mL pantoprazole oral suspension may be made with pantoprazole tablets, sterile water, and sodium bicarbonate powder. Remove the Protonix imprint from twenty 40 mg tablets with a paper towel dampened with ethanol (improves the look of product). Let tablets air dry. Crush the tablets in a mortar and reduce to a fine powder. Transfer to a 600 mL beaker, and add 340 mL sterile water. Place beaker on a magnetic stirrer. Add 16.8 g of sodium bicarbonate powder and stir for about 20 minutes until the tablet remnants have disintegrated. While stirring, add another 16.8 g of sodium bicarbonate powder and stir for about 5 minutes until powder has dissolved. Add enough sterile water for irrigation to bring the final volume to 400 mL. Mix well. Transfer to amber-colored bottle. Label "shake well" and "refrigerate". Stable for 62 days refrigerated.
Pack (Pantoprazole Sodium Oral)
40 mg (per each): $16.99
Pack (Protonix Oral)
40 mg (per each): $19.84
Solution (reconstituted) (Pantoprazole Sodium Intravenous)
40 mg (per each): $3.36 - $85.00
Solution (reconstituted) (Protonix Intravenous)
40 mg (per each): $6.09
Tablet, EC (Pantoprazole Sodium Oral)
20 mg (per each): $0.43 - $10.79
40 mg (per each): $4.06 - $10.79
Tablet, EC (Protonix Oral)
20 mg (per each): $19.93
40 mg (per each): $19.93
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