Protonix

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

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Protonix is a prescription medication used for:

• erosive esophagitis (damage to the esophagus caused by stomach acid) caused by gastroesophageal reflux disease (GERD)
• Zollinger-Ellison Syndrome (a condition in which the stomach makes too much acid)

​This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Do not take Protonix if you are:

• allergic to any of the ingredients in Protonix. 
• allergic to any proton pump inhibitor (PPI). If you do not know if your medicines are PPIs, please ask your doctor.

Pantoprazole is used to treat certain conditions in which there is too much acid in the stomach. It is used to treat erosive esophagitis or "heartburn" caused by gastroesophageal reflux disease (GERD), a condition where the acid in the stomach washes back up into the esophagus. This medicine may also be used to treat Zollinger-Ellison syndrome, a condition where the stomach produces too much acid.

Pantoprazole is a proton pump inhibitor (PPI). It works by decreasing the amount of acid produced by the stomach.

This medicine is available only with your doctor's prescription.

Protonix I.V.: 40 mg pantoprazole white to off-white freeze-dried powder in a single-dose vial for reconstitution.

Presence of Gastric Malignancy

In adults, symptomatic response to therapy with Protonix I.V. does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. In older patients, also consider an endoscopy.

Hypersensitivity and Severe Skin Reactions

Anaphylaxis and other serious reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN) have been reported with use of Protonix I.V. These may require emergency medical treatment [see Adverse Reactions (6.2)].

Injection Site Reactions

Thrombophlebitis was associated with the administration of Protonix I.V.

Potential for Exacerbation of Zinc Deficiency

Protonix I.V. contains edetate disodium (the salt form of EDTA), a chelator of metal ions including zinc. Therefore, zinc supplementation should be considered in patients treated with Protonix I.V. who are prone to zinc deficiency. Caution should be used when other EDTA containing products are also co-administered intravenously [see Dosage and Administration (2.5)].

Acute Interstitial Nephritis

Acute interstitial nephritis has been observed in patients taking PPIs including Protonix I.V. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue Protonix I.V. if acute interstitial nephritis develops [see Contraindications (4)].

Clostridium difficile-Associated Diarrhea

Published observational studies suggest that PPI therapy like Protonix I.V. may be associated with an increased risk of Clostridium difficile-associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions (6.2)].

Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.

Bone Fracture

Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration (2.2, 2.4) and Adverse Reactions (6)].

Cutaneous and Systemic Lupus Erythematosus

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including pantoprazole sodium. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematous cases were CLE.

The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement.

Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported.

Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving Protonix I.V., discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g. ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations.

Hepatic Effects

Mild, transient transaminase elevations have been observed in clinical studies. The clinical significance of this finding in a large population of subjects administered Protonix I.V. is unknown [see Adverse Reactions (6)].

Hypomagnesemia

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, and in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.

For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2)].

Interference with Urine Screen for THC

Pantoprazole sodium may produce false-positive urine screen for THC (tetrahydrocannabinol) [see Drug Interactions (7)].

Concomitant Use of Protonix I.V. with Methotrexate

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients [see Drug Interactions (7)].

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

A multicenter, double-blind, two-period placebo-controlled study was conducted to assess the ability of Protonix I.V. to maintain gastric acid suppression in patients switched from Protonix Delayed-Release Tablets to Protonix I.V. GERD patients (n=65, 26 to 64 years; 35 female; 9 Black, 11 Hispanic, 44 White, 1 other) with a history of EE were randomized to receive either 20 or 40 mg of oral pantoprazole once per day for 10 days (period 1), and then were switched in period 2 to either daily Protonix I.V. or placebo for 7 days, matching their respective dose level from period 1. Patients were administered all test medication with a light meal. Maximum acid output (MAO) and basal acid output (BAO) were determined 24 hours following the last day of oral medication (day 10), the first day (day 1) of intravenous administration and the last day of intravenous administration (day 7). MAO was estimated from a 1 hour continuous collection of gastric contents following subcutaneous injection of 6.0 mcg/kg of pentagastrin.

This study demonstrated that, after 10 days of repeated oral administration followed by 7 days of intravenous administration, the oral and intravenous dosage forms of Protonix 40 mg are similar in their ability to suppress MAO and BAO in patients with GERD and a history of EE (see Table 4). Also, patients on oral Protonix who were switched to intravenous placebo experienced a significant increase in acid output within 48 hours of their last oral dose (see Table4). However, at 48 hours after their last oral dose, patients treated with Protonix I.V. had a significantly lower mean basal acid output (see Table4) than those treated with placebo.

To evaluate the effectiveness of Protonix I.V. as an initial treatment to suppress gastric acid secretion, two studies were conducted.

Study 1 was a multicenter, double-blind, placebo-controlled, study of the pharmacodynamic effects of Protonix I.V. and Protonix Delayed-Release Tablets. Patients with GERD and a history of EE (n=78, 20 to 67 years; 39 females; 7 Black, 19 Hispanic, 52 White) were randomized to receive either 40 mg Protonix I.V., 40 mg Protonix Delayed-Release Tablets, or placebo once daily for 7 days. Following an overnight fast, test medication was administered and patients were given a light meal within 15 minutes. MAO and BAO were determined 24 hours following the last day of study medication. MAO was estimated from a 1 hour continuous collection of gastric contents following subcutaneous injection of 6.0 mcg/kg of pentagastrin to stimulate acid secretion. This study demonstrated that, after treatment for 7 days, patients treated with Protonix I.V. had a significantly lower MAO and BAO than those treated with placebo (p<0.001), and results were comparable to those of patients treated with Protonix Delayed-Release Tablets (see Table 5).

Study 2 was a single-center, double-blind, parallel-group study to compare the clinical effects of Protonix I.V. and Protonix Delayed-Release Tablets. Patients (n=45, median age 56 years, 21 males and 24 females) with acute endoscopically proven reflux esophagitis (Savary/Miller Stage II or III) with at least 1 of 3 symptoms typical for reflux esophagitis (acid eructation, heartburn, or pain on swallowing) were randomized to receive either 40 mg Protonix I.V. or 40 mg Protonix Delayed-Release Tablets once daily for 5 days. After the initial 5 days, all patients were treated with 40 mg oral pantoprazole daily to complete a total of 8 weeks of treatment. Symptom relief was assessed by calculating the daily mean of the sums of the average scores for these 3 symptoms and the daily mean of the average score for each of the symptoms separately. There was no significant difference in symptom relief between Protonix I.V. and Protonix Delayed-Release Tablets within the first 5 days. A repeat endoscopy after 8 weeks of treatment revealed that 20 out of 23 (87%) of the patients treated with Protonix I.V. plus Protonix Delayed-Release Tablets and 19 out of 22 (86%) of the patients treated with Protonix Delayed-Release Tablets had endoscopically proven healing of their esophageal lesions.

Data comparing Protonix I.V. to other PPIs (oral or intravenous) or H2 receptor antagonists (oral or intravenous) are limited, and therefore, are inadequate to support any conclusions regarding comparative efficacy.

Pathological Hypersecretion Associated with Zollinger-Ellison Syndrome

Two studies measured the pharmacodynamic effects of 6 day treatment with Protonix I.V. in patients with Zollinger-Ellison Syndrome (with and without multiple endocrine neoplasia type I). In one of these studies, an initial treatment with Protonix I.V. in 21 patients (29 to 75 years; 8 female; 4 Black, 1 Hispanic, 16 White) reduced acid output to the target level (less than or equal to 10 mEq/h) and significantly reduced H+ concentration and the volume of gastric secretions; target levels were achieved within 45 minutes of drug administration.

In the other study of 14 patients (38 to 67 years; 5 female; 2 Black, 12 White) with Zollinger-Ellison Syndrome, treatment was switched from an oral PPI to Protonix I.V. Protonix I.V. maintained or improved control of gastric acid secretion.

In both studies, total doses of 160 or 240 mg per day of Protonix I.V., administered in divided doses, maintained basal acid secretion below target levels in all patients. Target levels were 10 mEq/hour in patients without prior gastric surgery, and 5 mEq/h in all patients with prior gastric acid-reducing surgery. Once gastric acid secretion was controlled, there was no evidence of tolerance during this 7 day study. Basal acid secretion was maintained below target levels for at least 24 hours in all patients and through the end of treatment in these studies (3 to 7 days) in all but 1 patient who required a dose adjustment guided by acid output measurements until acid control was achieved. In both studies, doses were adjusted to the individual patient need, but gastric acid secretion was controlled in greater than 80% of patients by a starting regimen of 80 mg every 12 hours.

You should not use Protonix if you are allergic to pantoprazole or to any other benzimidazole medication such as albendazole (Albenza), or mebendazole (Vermox).

Call your doctor at once if you have symptoms of a serious side effect: decreased urination, blood in your urine, severe stomach pain, watery or bloody diarrhea, or new or worsening symptoms of joint pain or a skin rash that worsens in sunlight.

Protonix is not for immediate relief of heartburn symptoms. Heartburn is often confused with the first symptoms of a heart attack. Seek emergency medical attention if you have chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, and a general ill feeling.

Take Protonix for the full prescribed length of time. Your symptoms may improve before the condition is fully treated.

Protonix should not be taken together with atazanavir (Reyataz) or nelfinavir (Viracept). Tell your doctor if you are taking either of these medications to treat HIV or AIDS.

Some conditions must be treated long-term with Protonix. Chronic use has caused stomach cancer in animal studies, but it is not known if this medication would have the same effects in humans. Talk with your doctor about your specific risk of developing stomach cancer.

Long-term treatment with Protonix may also make it harder for your body to absorb vitamin B-12, resulting in a deficiency of this vitamin. Talk with your doctor if you need long-term Protonix treatment and you have concerns about vitamin B-12 deficiency.

Heartburn is often confused with the first symptoms of a heart attack. Seek emergency medical attention if you have chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, and a general ill feeling.

You should not use this medicine if:

• you are allergic to pantoprazole or to similar medicines such as lansoprazole (Prevacid), esomeprazole (Nexium), omeprazole (Prilosec, Zegerid), or rabeprazole (AcipHex); or

• you also take medicine that contains rilpivirine (Edurant, Complera, Odefsey).

To make sure Protonix is safe for you, tell your doctor if you have:

• severe liver disease;

• low levels of magnesium in your blood;

• lupus;

• osteoporosis; or

• low bone mineral density (osteopenia).

Taking a proton pump inhibitor such as pantoprazole may increase your risk of bone fracture in the hip, wrist, or spine. This effect has occurred mostly in people who have taken the medicine long term or at high doses, and in those who are age 50 and older.

It is not known whether pantoprazole will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Pantoprazole can pass into breast milk and may harm a nursing baby. You should not breast-feed while using this medicine.

Protonix is not approved for use by anyone younger than 5 years old.