(pantoprazole sodium)

Prescribing Information
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5 WARNINGS AND PRECAUTIONS

5 WARNINGS AND PRECAUTIONS

5.1 Presence of Gastric Malignancy

In adults, symptomatic response to therapy with PROTONIX 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.

5.2 Acute Tubulointerstitial Nephritis

Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and 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 (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue PROTONIX and evaluate patients with suspected acute TIN [see Contraindications (4)].

5.3 Clostridium difficile-Associated Diarrhea

Published observational studies suggest that PPI therapy like PROTONIX 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.

5.4 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), Adverse Reactions (6.2)].

5.5 Severe Cutaneous Adverse Reactions

Severe cutaneous adverse reactions, including erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs [see Adverse Reactions (6.2)]. Discontinue PROTONIX at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.

5.6 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, 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.

5.7 Cyanocobalamin (Vitamin B-12) Deficiency

Generally, daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (Vitamin B-12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed.

5.8 Hypomagnesemia and Mineral Metabolism

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. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. 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)].

Consider monitoring magnesium and calcium levels prior to initiation of PROTONIX and periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism). Supplement with magnesium and/or calcium as necessary. If hypocalcemia is refractory to treatment, consider discontinuing the PPI.

5.9 Tumorigenicity

Due to the chronic nature of GERD, there may be a potential for prolonged administration of PROTONIX. In long-term rodent studies, pantoprazole was carcinogenic and caused rare types of gastrointestinal tumors. The relevance of these findings to tumor development in humans is unknown [see Nonclinical Toxicology (13.1)].

5.10 Fundic Gland Polyps

PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated.

5.11 Interference with Investigations for Neuroendocrine Tumors

Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Healthcare providers should temporarily stop PROTONIX treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary [see Clinical Pharmacology (12.2)].

5.12 Interference with Urine Screen for THC

There have been reports of false-positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs, including PROTONIX [see Drug Interactions (7)].

5.13 Concomitant Use of PROTONIX 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)].

Medication Guide

MEDICATION GUIDE

MEDICATION GUIDE
PROTONIX (pro-TAH-nix)
(pantoprazole sodium)
delayed-release tablets
and
PROTONIX (pro-TAH-nix)
(pantoprazole sodium)
for delayed-release oral suspension

What is the most important information I should know about PROTONIX?
You should take PROTONIX exactly as prescribed, at the lowest dose possible and for the shortest time needed.
PROTONIX may help your acid-related symptoms, but you could still have serious stomach problems. Talk with your doctor.
PROTONIX can cause serious side effects, including:

•
A type of kidney problem (acute tubulointerstitial nephritis). Some people who take proton pump inhibitor (PPI) medicines, including PROTONIX, may develop a kidney problem called acute tubulointerstitial nephritis that can happen at any time during treatment with PROTONIX. Call your doctor right away if you have a decrease in the amount that you urinate or if you have blood in your urine.
•
Diarrhea caused by an infection (Clostridium difficile) in your intestines. Call your doctor right away if you have watery stools or stomach pain that does not go away. You may or may not have a fever.
•
Bone fractures (hip, wrist, or spine). Bone fractures in the hip, wrist, or spine may happen in people who take multiple daily doses of PPI medicines and for a long period of time (a year or longer). Tell your doctor if you have a bone fracture, especially in the hip, wrist, or spine.
•
Certain types of lupus erythematosus. Lupus erythematosus is an autoimmune disorder (the body's immune cells attack other cells or organs in the body). Some people who take PPI medicines, including PROTONIX, may develop certain types of lupus erythematosus or have worsening of the lupus they already have. Call your doctor right away if you have new or worsening joint pain or a rash on your cheeks or arms that gets worse in the sun.
•
Low magnesium and other mineral levels in your body can happen in people who have taken PROTONIX for at least 3 months. Tell your doctor if you have symptoms of low magnesium levels, including seizures, dizziness, irregular heartbeat, jitteriness, muscle aches or weakness, and spasms of hands, feet or voice.

Talk to your doctor about your risk of these serious side effects.
PROTONIX can have other serious side effects. See "What are the possible side effects of PROTONIX?"

What is PROTONIX?
A prescription medicine called a proton pump inhibitor (PPI) used to reduce the amount of acid in your stomach.
In adults, PROTONIX is used for:

•
up to 8 weeks for the healing and symptom relief of acid-related damage to the lining of the esophagus (called erosive esophagitis or EE). Your doctor may prescribe another 8 weeks of PROTONIX in patients whose EE does not heal.
•
maintaining healing of EE and to help prevent the return of heartburn symptoms caused by GERD. It is not known if PROTONIX is safe and effective when used for longer than 12 months for this purpose.
•
the long-term treatment of conditions where your stomach makes too much acid. This includes a rare condition called Zollinger-Ellison Syndrome.

In children 5 years of age and older, PROTONIX is used for:

•
up to 8 weeks for the healing and symptom relief of EE.
It is not known if PROTONIX is safe if used longer than 8 weeks in children.

PROTONIX is not for use in children under 5 years of age.
It is not known if PROTONIX is safe and effective in children for treatment other than EE.

Do not take PROTONIX if you are:

•
allergic to pantoprazole sodium, any other PPI medicine, or any of the ingredients in PROTONIX. See the end of this Medication Guide for a complete list of ingredients.
•
taking a medicine that contains rilpivirine (EDURANT, COMPLERA, ODEFSEY, JULUCA) used to treat HIV-1 (Human Immunodeficiency Virus).

Before taking PROTONIX, tell your doctor about all of your medical conditions, including if you:

•
have low magnesium levels, low calcium levels and low potassium levels in your blood.
•
are pregnant or plan to become pregnant. PROTONIX may harm your unborn baby. Tell your doctor if you become pregnant or think you may be pregnant during treatment with PROTONIX.
•
are breastfeeding or plan to breastfeed. PROTONIX can pass into your breast milk. Talk with your doctor about the best way to feed your baby if you take PROTONIX.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Especially tell your doctor if you take methotrexate (Otrexup, Rasuvo, Trexall, XATMEP), digoxin (LANOXIN), or a water pill (diuretic).

How should I take PROTONIX?

•
Take PROTONIX exactly as prescribed by your doctor.
PROTONIX delayed-release tablets (PROTONIX tablets):
o
Do not split, chew, or crush PROTONIX tablets.
o
Swallow PROTONIX tablets whole, with or without food.
o
Tell your doctor if you are not able to swallow your PROTONIX tablet.
 
PROTONIX for delayed-release oral suspension (PROTONIX for oral suspension):
o
You may use antacids while taking PROTONIX tablets.
o
Do not split, chew, or crush PROTONIX for oral suspension.
o
Take PROTONIX for oral suspension about 30 minutes before a meal.
o
PROTONIX for oral suspension should only be given by mouth mixed in apple juice or applesauce or through a nasogastric (NG) tube or gastrostomy tube mixed in apple juice. Do not mix PROTONIX for oral suspension in liquids other than apple juice or foods other than applesauce.
o
Do not divide a packet of PROTONIX for oral suspension to make a smaller dose.
o
See the "Instructions for Use" at the end of this Medication Guide for instructions on how to mix and take PROTONIX for oral suspension by mouth in applesauce or apple juice or how to mix and give the suspension through an NG tube or gastrostomy tube mixed in apple juice.
•
If you miss a dose of PROTONIX, take it as soon as possible. If it is almost time for your next dose, do not take the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time.
•
If you take too much PROTONIX, call your doctor or your poison control center at 1-800-222-1222 right away or go to the nearest emergency room.

What are the possible side effects of PROTONIX?
PROTONIX can cause serious side effects, including:

•
See "What is the most important information I should know about PROTONIX?"
•
Low vitamin B-12 levels in your body can happen in people who have taken PROTONIX for a long time (more than 3 years). Tell your doctor if you have symptoms of low vitamin B-12 levels, including shortness of breath, lightheadedness, irregular heartbeat, muscle weakness, pale skin, feeling tired, mood changes, and tingling or numbness in the arms and legs.
•
Stomach growths (fundic gland polyps). People who take PPI medicines for a long time have an increased risk of developing a certain type of stomach growths called fundic gland polyps, especially after taking PPI medicines for more than 1 year.
•
Severe skin reactions. PROTONIX can cause rare but severe skin reactions that may affect any part of your body. These serious skin reactions may need to be treated in a hospital and may be life threatening:
o
Skin rash which may have blistering, peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands or feet).
o
You may also have fever, chills, body aches, shortness of breath, or enlarged lymph nodes.

Stop taking PROTONIX and call your doctor right away. These symptoms may be the first sign of a severe skin reaction.
The most common side effects of PROTONIX in adults include: headache, diarrhea, nausea, stomach-area (abdominal) pain, vomiting, gas, dizziness, and joint pain.
The most common side effects of PROTONIX in children include: upper respiratory infection, headache, fever, diarrhea, vomiting, rash, and stomach-area (abdominal) pain.
These are not all the possible side effects of PROTONIX. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store PROTONIX?
Store PROTONIX at room temperature between 68°F to 77°F (20°C to 25°C).
Keep PROTONIX and all medicines out of the reach of children.

General information about the safe and effective use of PROTONIX.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use PROTONIX for a condition for which it was not prescribed. Do not give PROTONIX to other people, even if they have the same symptoms that you have. It may harm them. You can ask your doctor or pharmacist for information about PROTONIX that is written for health professionals.

What are the ingredients in PROTONIX?
Active ingredient: pantoprazole sodium sesquihydrate
Inactive ingredients in PROTONIX delayed-release tablets: calcium stearate, crospovidone, hypromellose, iron oxide, mannitol, methacrylic acid copolymer, polysorbate 80, povidone, propylene glycol, sodium carbonate, sodium lauryl sulfate, titanium dioxide, and triethyl citrate.
Inactive ingredients in PROTONIX for delayed-release oral suspension: crospovidone, hypromellose, methacrylic acid copolymer, microcrystalline cellulose, polysorbate 80, povidone, sodium carbonate, sodium lauryl sulfate, talc, titanium dioxide, triethyl citrate, and yellow ferric oxide.
For more information go to www.pfizer.com or call 1-800-438-1985.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

This product's label may have been updated. For the most recent prescribing information, please go to www.pfizer.com.

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under license from
Takeda GmbH
D78467 Konstanz, Germany

LAB-0574-16.0

Revised: March 2022

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