Hyperacidity, GERD, and ulcers:

Indications for: PROTONIX for ORAL SUSP

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).

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.

Adult Dosage:

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 Dosage:

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.

PROTONIX for ORAL SUSP Contraindications:

Concomitant rilpivirine-containing products.

PROTONIX for ORAL SUSP 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.

See Also:

PROTONIX for ORAL SUSP Classification:

Proton pump inhibitor.

PROTONIX for ORAL SUSP 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.

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.

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.

Drug Elimination:

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

Generic Drug Availability:

YES

How Supplied:

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