Protonix For Oral Susp

— THERAPEUTIC CATEGORIES —
  • Hyperacidity, GERD, and ulcers
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Protonix For Oral Susp Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Pantoprazole (as sodium) 40mg; per pkt; e-c del-rel granules.

    Pharmacological Class

    Proton pump inhibitor.

    See Also

    How Supplied

    Tabs—90; Susp—30 packets; Vials—1, 10, 25

    How Supplied

    Protonix for Delayed-Release Oral Suspension

    • Supplied  as pale yellowish to dark brownish, enteric-coated granules containing 40 mg pantoprazole in a unit-dose packet and available in 30 unit-dose cartons.

    Storage

    Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).

    Manufacturer

    Pfizer Inc.

    Generic Availability

    YES

    Mechanism of Action

    Pantoprazole suppresses the final step in gastric acid production by covalently binding to the (H+, K+)-ATPase enzyme system at the secretory surface of the gastric parietal cell.

    Protonix For Oral Susp Indications

    Indications

    Short-term treatment (up to 8 weeks) and maintenance of healing of erosive esophagitis (EE). Long-term treatment of pathological hypersecretory conditions (eg, Zollinger-Ellison syndrome).

    Protonix For Oral Susp Dosage and Administration

    Adult

    Swallow whole. Do not crush or chew granules. Susp: Take 30mins before a meal. Mix contents of packet in 5mL of apple juice or applesauce (do not mix in water, other liquids or foods); then swallow. May give via NG or gastrostomy tube (see full labeling). Treatment of EE: 40mg once daily for ≤8 weeks; if not healed, may repeat for 8 more weeks. Maintenance of EE healing: 40mg once daily. Hypersecretory conditions: initially 40mg twice daily; max 240mg/day.

    Children

    Swallow whole. Do not crush or chew granules. Susp: Take 30mins before a meal. Mix contents of packet in 5mL of apple juice or applesauce (do not mix in water, other liquids or foods); then swallow. May give via NG or gastrostomy tube (see full labeling). <5yrs: not recommended. Treatment of EE: Give once daily for up to 8 weeks. ≥5yrs: (≥15kg to <40kg): 20mg; (≥40kg): 40mg.

    Administration

    Administer in 1 teaspoonful of applesauce or apple juice approx. 30 minutes prior to meal. Do not crush or chew granules. Granules will not dissolve in apple juice. Take within 10mins of preparation. Packets cannot be divided to make a smaller dose. NG or gastrostomy tube: add 10mL of apple juice and gently tap and/or shake the barrel of the syringe to help rinse the syringe and tube. Repeat at least twice more using the same amount of apple juice (10mL) each time. No granules should remain in the syringe.

    Nursing Considerations

    Administer in 1 teaspoonful of applesauce or apple juice approx. 30 minutes prior to meal. Do not crush or chew granules. Granules will not dissolve in apple juice. Take within 10 minutes of preparation. Packets cannot be divided to make a smaller dose. NG or gastrostomy tube: add 10mL of apple juice and gently tap and/or shake the barrel of the syringe to help rinse the syringe and tube. Repeat at least twice more using the same amount of apple juice (10mL) each time. No granules should remain in the syringe. May use concomitant antacids.

    Protonix For Oral Susp Contraindications

    Contraindications

    Concomitant rilpivirine-containing products.

    Protonix For Oral Susp Boxed Warnings

    Not Applicable

    Protonix For Oral Susp Warnings/Precautions

    Warnings/Precautions

    Symptomatic response does not preclude gastric malignancy. Discontinue and evaluate if acute tubulointerstitial nephritis, severe cutaneous adverse reactions, or cutaneous/systemic lupus erythematosus occurs. Long-term therapy (eg, >3yrs) may lead to malabsorption/deficiency of Vit. B12. Monitor magnesium levels during prolonged therapy. Consider monitoring magnesium, calcium levels in those with preexisting risk of hypocalcemia (eg, hypoparathyroidism). Increased risk of fundic gland polyps with long-term use (esp. >1yr) or osteoporosis-related fractures (hip, wrist or spine) with long-term (>1yr) and multiple daily dose PPI therapy. Use lowest dose for shortest duration appropriate to condition. Reevaluate periodically. IV: consider zinc supplementation in those prone to zinc deficiency. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Presence of Gastric Malignancy

    • Symptomatic response does not preclude gastric malignancy. Consider additional follow-up and diagnostic testing in adults with suboptimal response or an early symptomatic relapse after completing treatment.

    • Consider endoscopy in older patients.

    Acute Tubulointerstitial Nephritis

    • Acute tubulointerstitial nephritis (TIN) may occur at any point during PPI therapy.

    • Signs and symptoms may vary from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function.

    • Discontinue and evaluate patients with suspected acute TIN.

    Clostridium difficile-Associated Diarrhea 

    • Protonix may be associated with a greater risk of Clostridium difficile associated diarrhea, especially in hospitalized patients.

    • Consider diagnosis of Clostridium difficile for diarrhea does not improve.

    • Use the lowest dose of Protonix and for the shortest duration of PPI therapy appropriate to the condition.

    Bone Fracture

    • PPI therapy may be associated with a greater risk of osteoporosis-related fractures of the hip, wrist, or spine.

    • Higher risk in patients who receive high-dose (multiply daily doses) and long-term PPI therapy (1 year or longer).

    • Use the lowest dose of Protonix and for the shortest duration of PPI therapy appropriate to the condition.

    Severe Cutaneous Adverse Reactions

    • PPI therapy have been associated with severe cutaneous adverse reactions (SCARs), including erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP).

    • Discontinue at the first sign or symptoms of SCARs or other signs of hypersensitivity and consider further evaluation.

    Cutaneous Lupus Erythematosus (CLE) and Systemic Lupus Erythematosus (SLE)

    • Cutaneous and systemic lupus erythematosus have been reported with PPI therapy; a majority of cases were CLE.

    • The most common form of CLE was subacute.

    • Avoid administering PPI therapy for longer than medically indicated.

    • Discontinue Protonix and refer to a specialist for evaluation if signs or symptoms consistent with CLE or SLE are observed. Most patients improved after discontinuing PPI in 4 to 12 weeks.

    Cyanocobalamin (Vitamin B-12) Deficiency  

    • Long-term therapy (eg, >3yrs) may lead to malabsorption/deficiency of Vit. B12. 

    Hypomagnesemia and Mineral Metabolism

    • Consider monitoring magnesium levels prior to initiation and periodically during treatment in patients expected to be on prolonged treatment, in patients who take concomitant medications (eg, digoxin) that may cause hypomagnesemia, and in patients with a preexisting risk of hypocalcemia (eg, hypoparathyroidism). 

    • Patients with preexisting risk of hypocalcemia will need magnesium and/or calcium supplementation. Consider discontinuing PPI therapy if hypocalcemia is refractory to treatment.

    Tumorigenicity

    • Prolonged administration of Protonix may be carcinogenic and cause rare types of GI tumors, according to long-term rodent studies. 

    • The relevance of these findings to tumor development in humans is unknown.

    Fundic Gland Polyps 

    • Increased risk of fundic gland polyps which increases with long-term use (especially beyond 1 year).

    • Patients were mostly asymptomatic and the fundic gland polyps were identified incidentally on endoscopy.

    • Use the shortest duration of PPI therapy.

    Interference with Investigations for Neuroendocrine Tumors 

    • Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity.

    • May cause false (+) results in diagnostic investigations for neuroendocrine tumors. 

    • Temporarily discontinue Protonix at least 14 days prior to CgA level assessment and consider repeating the test if initial CgA levels are high.

    Interference with Urine Screen for THC 

    • May cause false (+) urine THC test.

    Concomitant Use of Protonix with Methotrexate 

    • Concomitant use of PPI with high-dose methotrexate may potentiate serum levels of methotrexate and/or its metabolites and lead to toxicities.

    • Consider temporarily withdrawing the PPI therapy in patients receiving high-dose methotrexate.

    Pregnancy Considerations

    Risk Summary

    • Available data from published observational studies did not demonstrate an association of major malformations or other adverse pregnancy outcomes with pantoprazole.

    Nursing Mother Considerations

    Risk Summary

    • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for Protonix and any potential adverse effects on the breastfed child or from the underlying maternal condition.

    Pediatric Considerations

    • The efficacy and safety of Protonix for short-term treatment EE associated with GERD has been established in patients 1 year through 16 years of age. Efficacy of Protonix for EE associated with GERD in patients less than 1 year of age has not been established. There is also no appropriate dosage strength in an age-appropriate formulation available for patients less than 5 years of age.

    • The safety and effectiveness of Protonix for pediatric uses other than EE have not been established.  

    • 1 year through 16 years of age: The effectiveness of Protonix for treating symptomatic GERD in pediatric patients has not been established.

    • The use of Protonix for treatment of symptomatic GERD in infants less than 1 year of age is not indicated.

    Geriatric Considerations

    • The incidence rates of adverse reactions and laboratory abnormalities in patients aged 65 years and older were similar to those associated with patients younger than 65 years of age.

    Protonix For Oral Susp Pharmacokinetics

    Absorption

    • Peak plasma concentration after an oral 40 mg dose of Protonix tablet was reached in approximately 2.5 hours and the maximum concentration was 2.5 μg/mL.

    • Absolute bioavailability was 77%.

    • Food may delay absorption of Protonix tablets by up to 2 hours or longer; but this did not change the maximum concentration and the area under the curve for Protonix.

    Distribution

    • Apparent volume of distribution is approximately 11 to 23.6 L, mainly distributed in extracellular fluid.

    • ~98% serum protein bound, primarily to albumin.

    Metabolism

    • Extensively metabolized in the liver via CYP system.

    • Main metabolic pathway is demethylation by CYP2C19 with subsequent sulfation. Other metabolic pathways include oxidation by CYP3A4.

    Elimination

    Renal (71%), fecal (18%).

    Protonix For Oral Susp Interactions

    Interactions

    See Contraindications. May antagonize atazanavir, nelfinavir (avoid). May potentiate saquinavir, methotrexate (at high doses, consider temporary withdrawal of the PPI); monitor. May alter absorption of gastric pH-dependent drugs (eg, iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole, itraconazole). Caution with digoxin or drugs that may cause hypomagnesemia (eg, diuretics); monitor. Monitor warfarin. May cause false (+) results in diagnostic investigations for neuroendocrine tumors; discontinue pantoprazole 14 days prior to CgA level assessment. May cause false (+) urine THC test. IV: caution with concomitant other EDTA-containing products.

    Protonix For Oral Susp Adverse Reactions

    Adverse Reactions

    Headache, diarrhea, nausea, abdominal pain, vomiting, flatulence, dizziness, arthralgia; possible C. difficile-associated diarrhea, inj site reactions (IV); rare: hypomagnesemia and mineral metabolism. Also children: URI, fever, rash.

    Protonix For Oral Susp Clinical Trials

    Clinical Trials

    Erosive Esophagitis (EE) Associated with GERD 

    Adult Patients (Trial 1)

    • The approval was based on data from a US multicenter, double-blind, placebo-controlled study which evaluated the efficacy and safety of Protonix  in 603 patients with reflux symptoms and endoscopically diagnosed EE of grade 2 or above (Hetzel-Dent scale). Patients received either Protonix 10 mg, 20 mg, or 40 mg once daily, or placebo.

    • At week 4, 45.6%, 58.4% and 75.0% of patients treated with Protonix 10 mg, 20 mg, and 40 mg, respectively, achieved greater EE healing rates compared with 14.3% of those treated with placebo (all P <.001 vs placebo).

    • At week 8, 66.0%, 83.5%, and 92.6% of patients treated with Protonix 10 mg, 20 mg, and 40 mg, respectively, achieved greater EE healing rates compared with 39.7% of those treated with placebo (all P <.001 vs placebo).

    • At both weeks 4 and 8, treatment with Protonix 40 mg had significantly greater healing rates vs Protonix 10 mg or 20 mg (P <.05), and Protonix 20 mg had significantly greater healing rates vs Protonix 10 mg (P <.05).

    • A significantly greater proportion of patients who received Protonix 40 mg experienced complete relief of daytime and nighttime heartburn and the absence of regurgitation, starting from the first day of treatment, compared with placebo.

    • There were fewer antacid tablets per day consumed among patients who received Protonix compared with those who received placebo.

    Adult Patients (Trial 2)

    • In a US multicenter, double-blind study, Protonix 20 mg and 40 mg once daily were compared with nizatidine 150 mg twice daily in 243 patients with reflux symptoms and endoscopically diagnosed EE of grade 2 or above.

    • At week 4, 61.4% and 64.0% of patients treated with Protonix 20 mg and 40 mg, respectively, achieved superior EE healing rates compared with 22.2% of those treated with nizatidine 150 mg (both P <.001).

    • At week 8, 79.2% and 82.9% of patients treated with Protonix 20 mg and 40 mg, respectively, achieved superior EE healing rates compared with 41.4% of those treated with nizatidine 150 mg (both P <.001).

    • A significantly greater proportion of patients who received Protonix 40 mg experienced complete relief of nighttime heartburn and regurgitation, starting on the first day and of daytime heartburn on the second day, compared with those taking nizatidine 150 mg twice daily.

    • There were fewer antacid tablets per day consumed among patients who received Protonix compared with those who received nizatidine.

    Pediatric Patients Aged 5 Years through 16 Years

    • The efficacy of Protonix in pediatric patients 5 to 16 years of age was extrapolated from adequate and well-controlled trials in adults.

    • There were 4 pediatric patients with endoscopically diagnosed EE  who were evaluated in multicenter, randomized, double-blind, parallel-treatment trials. Patients were treated with Protonix 20 mg or 40 mg once daily for 8 weeks. All 4 patients with EE were healed at 8 weeks, defined as a Hetzel-Dent score of 9 or 1.

     

    Long-Term Maintenance of Healing of Erosive Esophagitis

    • Approval was based on 2 US independent, multicenter, randomized, double-blind, comparator-controlled trials (386 and 404 patients, respectively) in adult GERD patients with endoscopically confirmed healed EE.

    • Patients received either Protonix 10 mg, 20 mg, or 40 mg delayed-release tablets once daily or ranitidine 150 mg twice daily.

    • Protonix 20 mg and 40 mg was significantly superior to ranitidine at every time point (Month 1, 3, 6, and 12) for the maintenance of healing

    • Protonix 40 mg achieved superiority to ranitidine in reducing the number of daytime and nighttime heartburn episodes from Month 1 to 12 of treatment.

    • Protonix 20 mg was also effective in reducing episodes of daytime and nighttime heartburn in one trial.

     

    Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome  

    • Approval was based on a multicenter, open-label trial which included 35 patients with pathological hypersecretory conditions, such as Zollinger-Ellison Syndrome, with or without multiple endocrine neoplasia-type I.

    • Treatment with Protonix ranging from 80 mg to 240 mg daily successfully controlled gastric acid secretion and maintained gastric acid output below 10 mEq/h in patients without prior acid-reducing surgery and below 5 mEq/h in patients with prior acid-reducing surgery.

    Protonix For Oral Susp Note

    Not Applicable

    Protonix For Oral Susp Patient Counseling

    Patient Counseling

    Gastric Malignancy 

    • Return to your healthcare provider if you have a suboptimal response or an early symptomatic relapse.

    Acute Tubulointerstitial Nephritis

    • Call your healthcare provider immediately if you experience signs and/or symptoms associated with acute tubulointerstitial nephritis.

    Clostridium difficile-Associated Diarrhea

    • Immediately call your healthcare provider if you experience diarrhea that does not improve.

    Bone Fracture

    • Report any fractures, especially of the hip, wrist or spine, to their healthcare provider.

    Severe Cutaneous Adverse Reactions 

    • Discontinue Protonix and immediately call your healthcare provider for further evaluation. 

    Cutaneous and Systemic Lupus Erythematosus 

    • Immediately call your healthcare provider for any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus.

    Cyanocobalamin (Vitamin B-12) Deficiency 

    • Report any clinical symptoms that may be associated with cyancobalamin deficiency to a healthcare provider if you have been receiving Protonix for longer than 3 years. 

    Hypomagnesemia and Mineral Metabolism 

    • Report any clinical symptoms that may be associated with hypomagnesemia, hypocalcemia, and/or hypokalemia, to a healthcare provider, if you have been receiving Protonix for at least 3 months. 

    Drug Interactions 

    • Inform healthcare provider of any other medications if you are currently taking, including rilpivirine-containing products, digoxin and high dose methotrexate. 

    Pregnancy 

    • Advise a pregnant woman of the potential risk to a fetus. Inform healthcare provider of a known or suspected pregnancy.

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