Protonix (pantoprazole sodium) - 3 indications

Scroll down for more information on each indication:

• for the short-term treatment of erosive esophagitis associated with gastroesophageal reflux disease (GERD); approved February 2000
• for the maintenance of healing of erosive esophagitis; approved June 2001
• for the treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome; approved April 2002

General Information

Protonix (pantoprazole sodium) is an acid suppressant.

Protonix is specifically indicated for the following:

• the short-term treatment (up to 8 weeks) of erosive esophagitis associated with gastroesophageal reflux disease (GERD) in adults and pediatric patients five years of age and older 
• the maintenance of healing of erosive esophagitis and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with GERD.
• for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome

Protonix is supplied as a delayed-release tablet, a delayed-release oral suspension and as an intravenous solution.

Protonix Delayed-Release Tablets

• Swallow tablets whole, with or without food in the stomach. For patients unable to swallow a 40 mg tablet, two 20 mg tablets may be taken. Concomitant administration of antacids does not affect the absorption of Protonix Delayed-Release Tablets

Protonix For Delayed-Release Oral Suspension

• Administer Protonix For Delayed-Release Oral Suspension approximately 30 minutes prior to a meal via oral administration in apple juice or applesauce or nasogastric tube in apple juice only. Because proper pH is necessary for stability, do not administer Protonix For Delayed-Release Oral Suspension in liquids other than apple juice, or foods other than applesauce.
• Do not divide the 40 mg Protonix For Delayed-Release Oral Suspension packet to create a 20 mg dosage for pediatric patients who are unable to take the tablet formulation.

Scroll down for the recommended dosing/administration for each indication.

Mechanism of Action

Pantoprazole is a proton pump inhibitor (PPI) that suppresses the final step in gastric acid production by forming a covalent bond to two sites of the (H+, K+)-ATPase enzyme system at the secretory surface of the gastric parietal cell. This effect is dose-related and leads to inhibition of both basal and stimulated gastric acid secretion irrespective of the stimulus. The binding to the (H+, K+)-ATPase results in a duration of antisecretory effect that persists longer than 24 hours. 

Side Effects

Adverse effects associated with the use of Protonix in adults may include, but are not limited to, the following:

• headache
• diarrhea
• nausea
• abdominal pain
• vomiting
• flatulence
• dizziness
• arthralgia

Adverse effects associated with the use of Protonix in pediatrics may include, but are not limited to, the following:

• headache
• fever
• diarrhea
• vomiting
• rash
• abdominal pain

Indication 1 - the short-term treatment of erosive esophagitis associated with GERD

approved February 2000

Dosing/Administration

Tablets

Adults: 40 mg once daily for up to 8 weeks. For adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of may be considered.

Children 5 years and older: 

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

 Intravenous Infusion

The recommended adult dosage is 40 mg given once daily by intravenous infusion for 7 to 10 days

Clinical Trial Results

Adult Patients

A US multicenter, double-blind, placebo-controlled study of Protonix 10 mg, 20 mg, or 40 mg once daily was conducted in 603 patients with reflux symptoms and endoscopically diagnosed EE of grade 2 or above (Hetzel-Dent scale). In this study, approximately 25% of enrolled patients had severe EE of grade 3, and 10% had grade 4. In this study, all Protonix treatment groups had significantly greater healing rates than the placebo group. This was true regardless of H. pylori status for the 40 mg and 20 mg Protonix treatment groups. The 40 mg dose of Protonix resulted in healing rates significantly greater than those found with either the 20 mg or 10 mg dose.

A significantly greater proportion of patients taking 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. Patients taking Protonix consumed significantly fewer antacid tablets per day than those taking placebo.

The percentages of patients healed (per protocol, n = 541) in this study are shown below:

Week	10 mg daily (n = 153)	20 mg daily (n = 158)	40 mg daily (n = 162)	Placebo
4	45.6%	58.4%	75.0%	14.3%
8	66.0%	83.5%	92.6%	39.7%

Pediatric Patients Ages 5 Years through 16 Years

The efficacy of Protonix in the treatment of EE associated with GERD in pediatric patients ages 5 years through 16 years is extrapolated from adequate and well-conducted trials in adults, as the pathophysiology is thought to be the same. Four pediatric patients with endoscopically diagnosed EE were studied in multicenter, randomized, double-blind, parallel-treatment trials. Children with endoscopically diagnosed EE (defined as an endoscopic Hetzel-Dent score ≥2) were treated once daily for 8 weeks with one of two dose levels of Protonox (20 mg or 40 mg). All 4 patients with EE were healed (Hetzel-Dent score of 0 or 1) at 8 weeks.

Indication 2 - the maintenance of healing of erosive esophagitis

approved June 2001

Dosing/Administration

The recommended adult dosage is 40 mg given once daily. Controlled studies did not extend beyond 12 months.

Clinical Trial Results

Two independent, multicenter, randomized, double-blind, comparator-controlled trials of identical design were conducted in adult GERD patients with endoscopically confirmed healed EE to demonstrate efficacy of Protonix in long-term maintenance of healing. The two US studies enrolled 386 and 404 patients, respectively, to receive either 10 mg, 20 mg, or 40 mg of Protonix Delayed-Release Tablets once daily or 150 mg of ranitidine twice daily. Protonix 40 mg and 20 mg were significantly superior to ranitidine at every timepoint with respect to the maintenance of healing. Patients were evaluated at Month 1, 3, 6 and 12. Protonix 40 mg was superior to ranitidine in reducing the number of daytime and nighttime heartburn episodes from the first through the twelfth month of treatment. Protonix 20 mg, administered once daily, was also effective in reducing episodes of daytime and nighttime heartburn in one trial. 

Indication 3 - for the treatment of pathological hypersecretory conditions

approved April 2002

Dosing/Administration

Tablets

The recommended adult dosage is 40 mg given twice daily. Dosage regimens should be adjusted to individual patient needs and should continue for as long as clinically indicated. Doses up to 240 mg daily have been administered.

Intravenous Infusion

The recommended adult dosage is 80 mg administered every 12 hours by intravenous infusion.

Clinical Trial Results

In a multicenter, open-label trial of 35 patients with pathological hypersecretory conditions, such as Zollinger-Ellison Syndrome, with or without multiple endocrine neoplasia-type I, Protonix successfully controlled gastric acid secretion. Doses ranging from 80 mg daily to 240 mg daily 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. 

Doses were initially titrated to the individual patient needs, and adjusted in some patients based on the clinical response with time. Protonix was well tolerated at these dose levels for prolonged periods (greater than 2 years in some patients).