(pantoprazole sodium)

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14 CLINICAL STUDIES

14 CLINICAL STUDIES

PROTONIX Delayed-Release Tablets were used in the following clinical trials.

14.1 Erosive Esophagitis (EE) Associated with Gastroesophageal Reflux Disease (GERD)

Adult Patients

A US multicenter, double-blind, placebo-controlled study of PROTONIX 10 mg, 20 mg, or 40 mg once daily was conducted in 603 patients with reflux symptoms and endoscopically diagnosed EE of grade 2 or above (Hetzel-Dent scale). In this study, approximately 25% of enrolled patients had severe EE of grade 3, and 10% had grade 4. The percentages of patients healed (per protocol, n = 541) in this study are shown in Table 8.

Table 8: Erosive Esophagitis Healing Rates (Per Protocol)
PROTONIXPlacebo
Week10 mg daily
(n = 153)		20 mg daily
(n = 158)		40 mg daily
(n = 162)		(n = 68)
*
(p < 0.001) PROTONIX versus placebo
†
(p < 0.05) versus 10 mg PROTONIX
‡
(p < 0.05) versus 10 mg or 20 mg PROTONIX

4

45.6%*

58.4%*†

75.0%*‡

14.3%

8

66.0%*

83.5%*†

92.6%*‡

39.7%

In this study, all PROTONIX treatment groups had significantly greater healing rates than the placebo group. This was true regardless of H. pylori status for the 40 mg and 20 mg PROTONIX treatment groups. The 40 mg dose of PROTONIX resulted in healing rates significantly greater than those found with either the 20 mg or 10 mg dose.

A significantly greater proportion of patients taking PROTONIX 40 mg experienced complete relief of daytime and nighttime heartburn and the absence of regurgitation, starting from the first day of treatment, compared with placebo. Patients taking PROTONIX consumed significantly fewer antacid tablets per day than those taking placebo.

PROTONIX 40 mg and 20 mg once daily were also compared with nizatidine 150 mg twice daily in a US multicenter, double-blind study of 243 patients with reflux symptoms and endoscopically diagnosed EE of grade 2 or above. The percentages of patients healed (per protocol, n = 212) are shown in Table 9.

Table 9: Erosive Esophagitis Healing Rates (Per Protocol)
PROTONIXNizatidine
Week20 mg daily
(n = 72)		40 mg daily
(n = 70)		150 mg twice daily
(n = 70)
*
(p < 0.001) PROTONIX versus nizatidine

4

61.4%*

64.0%*

22.2%

8

79.2%*

82.9%*

41.4%

Once-daily treatment with PROTONIX 40 mg or 20 mg resulted in significantly superior rates of healing at both 4 and 8 weeks compared with twice-daily treatment with 150 mg of nizatidine. For the 40 mg treatment group, significantly greater healing rates compared to nizatidine were achieved regardless of the H. pylori status.

A significantly greater proportion of the patients in the PROTONIX treatment groups experienced complete relief of nighttime heartburn and regurgitation, starting on the first day and of daytime heartburn on the second day, compared with those taking nizatidine 150 mg twice daily. Patients taking PROTONIX consumed significantly fewer antacid tablets per day than those taking nizatidine.

Pediatric Patients Ages 5 Years through 16 Years

The efficacy of PROTONIX in the treatment of EE associated with GERD in pediatric patients ages 5 years through 16 years is extrapolated from adequate and well-conducted trials in adults, as the pathophysiology is thought to be the same. Four pediatric patients with endoscopically diagnosed EE were studied in multicenter, randomized, double-blind, parallel-treatment trials. Children with endoscopically diagnosed EE (defined as an endoscopic Hetzel-Dent score ≥2) were treated once daily for 8 weeks with one of two dose levels of PROTONIX (20 mg or 40 mg). All 4 patients with EE were healed (Hetzel-Dent score of 0 or 1) at 8 weeks.

14.2 Long-Term Maintenance of Healing of Erosive Esophagitis

Two independent, multicenter, randomized, double-blind, comparator-controlled trials of identical design were conducted in adult GERD patients with endoscopically confirmed healed EE to demonstrate efficacy of PROTONIX in long-term maintenance of healing. The two US studies enrolled 386 and 404 patients, respectively, to receive either 10 mg, 20 mg, or 40 mg of PROTONIX Delayed-Release Tablets once daily or 150 mg of ranitidine twice daily. As demonstrated in Table 10, PROTONIX 40 mg and 20 mg were significantly superior to ranitidine at every timepoint with respect to the maintenance of healing. In addition, PROTONIX 40 mg was superior to all other treatments studied.

Table 10: Long-Term Maintenance of Healing of Erosive Gastroesophageal Reflux Disease (GERD Maintenance): Percentage of Patients Who Remained Healed
PROTONIX
20 mg daily		PROTONIX
40 mg daily		Ranitidine
150 mg twice daily
Note: PROTONIX 10 mg was superior (p <0.05) to ranitidine in Study 2, but not Study 1.
*
(p <0.05 vs. ranitidine)
†
(p <0.05 vs. PROTONIX 20 mg)

Study 1

n = 75

n = 74

n = 75

Month 1

91*

99*

68

Month 3

82*

93*†

54

Month 6

76*

90*†

44

Month 12

70*

86*†

35

Study 2

n = 74

n = 88

n = 84

Month 1

89*

92*†

62

Month 3

78*

91*†

47

Month 6

72*

88*†

39

Month 12

72*

83*

37

PROTONIX 40 mg was superior to ranitidine in reducing the number of daytime and nighttime heartburn episodes from the first through the twelfth month of treatment. PROTONIX 20 mg, administered once daily, was also effective in reducing episodes of daytime and nighttime heartburn in one trial, as presented in Table 11.

Table 11: Number of Episodes of Heartburn (mean ± SD)
PROTONIX
40 mg daily 		Ranitidine
150 mg twice daily
*
(p <0.001 vs. ranitidine, combined data from the two US studies)

Month 1

Daytime

5.1 ± 1.6*

18.3 ± 1.6

Nighttime

3.9 ± 1.1*

11.9 ± 1.1

Month 12

Daytime

2.9 ± 1.5*

17.5 ± 1.5

Nighttime

2.5 ± 1.2*

13.8 ± 1.3

14.3 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome

In a multicenter, open-label trial of 35 patients with pathological hypersecretory conditions, such as Zollinger-Ellison Syndrome, with or without multiple endocrine neoplasia-type I, PROTONIX successfully controlled gastric acid secretion. Doses ranging from 80 mg daily to 240 mg daily maintained gastric acid output below 10 mEq/h in patients without prior acid-reducing surgery and below 5 mEq/h in patients with prior acid-reducing surgery.

Doses were initially titrated to the individual patient needs, and adjusted in some patients based on the clinical response with time [see Dosage and Administration (2)]. PROTONIX was well tolerated at these dose levels for prolonged periods (greater than 2 years in some patients).

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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