Hyperacidity, GERD, and ulcers:

Indications for: PROTONIX IV

Short-term treatment (7–10 days) of GERD associated with a history of erosive esophagitis. Pathological hypersecretory conditions (eg, Zollinger-Ellison syndrome).

Clinical Trials:

Gastroesophageal Reflux Disease (GERD) Associated with a History of Erosive Esophagitis

Multicenter, double-blind, two-period placebo-controlled study

  • The study evaluated the ability of Protonix IV to maintain gastric acid suppression in patients switched from Protonix Delayed-Release Tablets to Protonix IV.

  • GERD patients with a history of EE were randomly assigned to receive either oral pantoprazole 20 mg or 40 mg once daily for 10 days (period 1), then were switched in period 2 to either daily Protonix IV or placebo for 7 days.

  • Maximum acid output (MAO) and basal acid output (BAO) were evaluated 24 hours following the last day of oral medication, the first day of IV administration and the last day of IV administration (day 7).

  • Results showed that the oral and IV dosage forms were similar in their ability to suppress MAO and BAO in patients with GERD and a history of EE.

Protonix IV as an initial treatment to suppress gastric acid secretion – Study 1

  • The study evaluated the pharmacodynamic effects of Protonix IV and Protonix Delayed-Release Tablets in patients with GERD and a history of EE.

  • Patients were randomly assigned to receive either Protonix 40 mg IV, Protonix Delayed-Release Tablets 40 mg, or placebo once daily for 7 days. MAO and BAO were evaluated 24 hours after the last day of study medication.

  • Patients treated with Protonix IV had significantly lower MAO and BAO vs placebo (P <.001), and were comparable to those patients who received Protonix Delayed-Release Tablets.

Protonix IV as an initial treatment to suppress gastric acid secretion – Study 2

  • The study evaluated the clinical effects of Protonix IV and Protonix Delayed-Release Tablets. 

  • Patients with acute endoscopically proven reflux esophagitis with at least 1 of 3 symptoms typical for reflux esophagitis (acid eructation, heartburn, or pain on swallowing) were randomized to receive either Protonix IV 40 mg or Protonix Delayed-Release Tablets 40 mg once daily for 5 days.

  • There was no significant difference in symptom relief between IV and tablet formulations within the first 5 days. 

 

Pathological Hypersecretion Associated with Zollinger-Ellison Syndrome 

  • 2 studies evaluated the pharmacodynamic effects of 6 day treatment with Protonix IV in patients with ZE Syndrome.

  • In one study, an initial treatment with Protonix IV reduced acid output to the target level of 10 mEq/h or less and significantly reduced H+ concentration and the volume of gastric secretions.

  • In the other study, patients who switched from oral PPI to Protonix IV had maintained or improved control of gastric acid secretion.

  • Both studies showed that Protonix IV maintained basal acid secretion below target levels in all patients. Once gastric acid secretion was controlled, there was no evidence of tolerance. Basal acid secretion was maintained below target levels for at least 24 hours in all patients and through the end of treatment.

Adult Dosage:

Give by IV infusion over 2mins or 15mins (see full labeling). ≥18yrs: GERD: 40mg once daily for 7–10 days; switch to tabs or oral suspension as soon as possible. Hypersecretory conditions: 80mg every 8–12hrs; usual max 240mg/day or 6 days' treatment.

Children Dosage:

<18yrs: not established.

PROTONIX IV Contraindications:

Concomitant rilpivirine-containing products.

PROTONIX IV 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 IV Classification:

Proton pump inhibitor.

PROTONIX IV 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%).

  • Total clearance is 7.6 to 14 L/h. 

  • Following the administration of Protonix IV, the serum concentration of pantoprazole declines biexponentially with a terminal elimination half-life of approximately 1 hour.

Generic Drug Availability:

YES

How Supplied:

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