pantoprazole (Rx)

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)

Cutaneous and systemic lupus erythematosus

Cyanocobalamin (vitamin B-12) deficiency

Clostridium difficile-associated diarrhea

Fundic gland polyps

Acute tubulointerstitial nephritis

Contraindications

Hypersensitivity to pantoprazole or other proton pump inhibitors (PPIs)

Concomitant administration with rilpivirine containing products

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

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) reported with PPIs; avoid using for longer than medically indicated; discontinue if signs or symptoms consistent with CLE or SLE are observed and refer patient to specialist; most patients improve with discontinuation of PPI alone in 4-12 weeks; serological testing (e.g. ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations

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

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; consider monitoring magnesium levels prior to initiation of PPI treatment and periodically

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; consider additional follow-up and diagnostic testing in adult patients who have suboptimal response or early symptomatic relapse after completing treatment with a PPI

Risk of salmonella and campylobacter infections increased with use of proton pump inhibitors

May elevate and/or prolong serum concentrations of methotrexate and/or its metabolite when administered concomitantly with PPIs, possibly leading to toxicity; consider a temporary withdrawal of PPI therapy with high dose methotrexate administration

PPI therapy is associated with increased risk of fundic gland polyp; risk increases with long-term use >1 year; patient may be asymptomatic; problem usually identified incidentally on endoscopy; use shortest duration of therapy appropriate to condition being treated

Acute tubulointerstitial nephritis (TIN) reported in patients taking PPIs; may occur at any point during PPI therapy; patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (eg, malaise, nausea, anorexia); in reported case series, some patients were diagnosed on biopsy and in absence of extra-renal manifestations (eg, fever, rash or arthralgia); discontinue therapy and evaluate patients with suspected acute TIN

Pregnancy

There are no adequate and well-controlled studies in pregnant women; advise pregnant women of the potential risk of fetal harm; drug should be used during pregnancy only if potential benefit justifies potential risk to fetus

Lactation

Pantoprazole and metabolites are excreted in milk of rats. Pantoprazole excretion in human milk has been detected in a study of a single nursing mother after a single 40 mg oral dose of pantoprazole sodium; clinical relevance of this finding not known; many drugs excreted in human milk have potential for serious adverse reactions in nursing infants; based on potential for tumorigenicity shown for pantoprazole sodium in rodent carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue drug, taking into account benefit of drug to mother

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.

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%)

Oral Administration

Switch IV patients to PO as soon as able to take tablets

Tablet should not be chewed or crushed

Administer before meals

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