Dosing and uses of Protonix (pantoprazole)
Adult dosage forms and strengths
oral suspension
- 40mg/packet
powder for injection
- 40mg/vial
tablet, delayed-release
- 20mg
- 40mg
Erosive Esophagitis Associated With GERD
Treatment: 40 mg PO qDay for 8-16 weeks
Maintenance of healing: 40 mg PO qDay
Alternatively, 40 mg IV qDay for 7-10 days
Short-term Treatment of GERD
Oral therapy inappropriate or not possible: 40 mg IV infusion over 15 minutes qDay for 7-10 days; switch to PO once patient able to swallow
Zollinger-Ellison Syndrome
40 mg PO qDay; up to 240 mg/day administered in some patients
80 mg IV infusion q8-12hr up to 7 days; switch to PO once patient able to swallow
Peptic Ulcer Disease (Off-label)
Duodenal ulcer: 40 mg PO qDay for 2 weeks
Gastric ulcer: 40 mg PO qDay for 4 weeks
Administration
Switch IV patients to PO as soon as able to take tablets
Tablet should not be chewed or crushed
Administer AC
Safety and efficacy for maintenance treatment past 1 year not established
Pediatric dosage forms and strengths
oral suspension
- 40mg/packet
tablet, delayed-release
- 20mg
- 40mg
Erosive Esophagitis Associated With GERD
<5 years
- Safety and efficacy not established
>5 years
- 15 kg to <40 kg: 20 mg PO qDay for up to 8 weeks
- 40 kg or greater: 40 mg PO qDay for up to 8 weeks
Protonix (pantoprazole) adverse (side) effects
1-10%
Headache (>4%)
Abdominal pain (4%)
Facial edema (<4%)
Generalized edema (<2%)
Chest pain (4%)
Diarrhea (4%)
Constipation (<4%)
Pruritus (4%)
Rash (4%)
Flatulence (<4%)
Hyperglycemia (1%)
Nausea (1%)
Vomiting (>4%)
Photosensitivity (<2%)
Frequency not defined
Angioedema
Atrophic gastritis
Anterior ischemic optic neuropathy
Hepatocellular damage leading to hepatic failure
Interstitial nephritis
Pancreatitis
Pancytopenia
Rhabdomyolysis
Risk of anaphylaxis
Stevens-Johnson syndrome
Fatal toxic epidermal necrolysis
Erythema multiforme
Postmarketing Reports
Asthenia, fatigue, malaise
Hepatocellular damage leading to jaundice and hepatic failure
Anaphylaxis (including anaphylactic shock)
Agranulocytosis, pancytopenia
Taste disorders (ageusia, dysgeusia)
Investigations: Weight changes
Hyponatremia, hypomagnesemia
Rhabdomyolysis, bone fracture
Hallucination, confusion, insomnia, somnolence
Interstitial nephritis
Severe dermatologic reactions (some fatal), including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis (some fatal), as well as angioedema (Quincke edema)
Warnings
Contraindications
Hypersensitivity to pantoprazole or other proton pump inhibitors (PPIs)
Cautions
PPIs are possibly associated with increased incidence of Clostridium difficile-associated diarrhea (CDAD); consider diagnosis of CDAD for patients taking PPIs who have diarrhea that does not improve
Severe hepatic impairment
Published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine, particularly with prolonged (>1 year), high-dose therapy
Decreased gastric acidity increases serum chromogranin A (CgA) levels and may cause false-positive diagnostic results for neuroendocrine tumors; temporarily discontinue PPIs before assessing CgA levels
PPIs may decrease the efficacy of clopidogrel by reducing the formation of the active metabolite
Gastric atrophy reported with long-term use of another PPI
Therapy increases risk of Salmonella, Campylobacter, and other infections
Hypomagnesemia may occur with prolonged use (>1 year); adverse effects may result, including tetany, arrhythmias, and seizures; in 25% of cases reviewed, magnesium supplementation alone did not improve low serum magnesium levels, and the PPI had to be discontinued
Infusion related reactions including thrombophlebitis and hypersensitivity reported
Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin
Acute interstitial nephritis reported in patients taking proton pump inhibitors
Relief of symptoms does not eliminate the possibility of a gastric malignancy
Risk of salmonella and campylobacter infections increased with use of proton pump inhibitors
Pregnancy and lactation
Pregnancy category: B
Lactation: Not known whether pantoprazole is distributed into breast milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Protonix (pantoprazole)
Mechanism of action
PPI; binds to H+/K+-exchanging ATPase (proton pump) in gastric parietal cells, resulting in blockage of acid secretion
Absorption
Bioavailability: 77% (PO; neither food nor antacid alters bioavailability)
Onset (PO PUD): 24 hr (initial response)
Duration (PO at steady state): 7 days (PUD)
Peak plasma time: 2.8 hr (PO); at end of infusion (IV)
Distribution
Protein bound: 98%
Vd: 11-24 L
Metabolism
Metabolized extensively by hepatic P450 enzyme CYP2C19; second pathway through CYP3A4
Slow metabolizers (3% of Caucasians and African Americans) are deficient in CPY2C19 enzyme system; plasma concentration can increase by 5-fold or more in comparison with that found in persons who have the enzyme
Metabolites: Desmethylpantoprazole sulfate conjugate (activity unknown)
Elimination
Half-life: 1 hr; increased to 3.5-10 hr with CYP2C19 deficiency
Dialyzable: No
Renal clearance: 0.1 L/hr/kg
Total body clearance: 7.6-14 L/hr
Excretion: Urine (71%); feces (18%)
Administration
IV Incompatibilities
Y-site: Midazolam, zinc solutions
IV Preparation
GERD with a history of erosive esophagitis
- 15-min infusion: Reconstitute with 10 mL NS, THEN further dilute with 100 mL D5W, NS, or LR to final concentration of 0.4 mg/mL
Zollinger-Ellison syndrome
- 15-min infusion: Reconstitute each vial with 10 mL NS, THEN
- Combine 2 vials and further dilute with 80 mL D5W, NS, or LR to total volume of 100 mL (concentration 0.8 mg/mL)
- 2-min injection: Reconstitute with 10 mL NS to final concentration of 4 mg/mL
IV Administration
Do not administer other IV solution simultaneously through same line
Use dedicated IV line or Y-site; stop Y-site administration if discoloration or precipitation
Infuse over 15 min no more than 3 mg/min (7 mL/min) for GERD and 6 mg/min (7 mL/min) for pathologic hypersecretory conditions
Storage
Reconstituted solution may be stored for 2 hr at room temperature before further dilution
Admixed solution may be stored for 12 hr at room temperature before administration
Store intact vials at 2-8°C (36-46°F); protect from light
