PANTOPRAZOLE SODIUM

PANTOPRAZOLE SODIUM- pantoprazole sodium tablet, delayed release
DirectRX

INDICATIONS & USAGE SECTION

Pantoprazole sodium delayed-release tablets are indicated for:

1.1 Short-Term Treatment of Erosive Esophagitis Associated With Gastroesophageal Reflux Disease (GERD)

Pantoprazole sodium delayed-release tablets are indicated in adults and pediatric patients five years of age and older for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis. For those adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole sodium delayed-release tablets may be considered. Safety of treatment beyond 8 weeks in pediatric patients has not been established.

1.2 Maintenance of Healing of Erosive Esophagitis

Pantoprazole sodium delayed-release tablets are indicated for maintenance of healing of erosive esophagitis and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with GERD. Controlled studies did not extend beyond 12 months.

1.3 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome

Pantoprazole sodium delayed-release tablets are indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

DOSAGE & ADMINISTRATION SECTION

• 2.1 Recommended Dosing Schedule

  Pantoprazole sodium is supplied as delayed-release tablets. The recommended dosages are outlined in Table 1.

  Table 1: Recommended Dosing Schedule for Pantoprazole Sodium Delayed-release Tablets

  *For adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole sodium delayed-release tablets may be considered.†Controlled studies did not extend beyond 12 months‡Dosage regimens should be adjusted to individual patient needs and should continue for as long as clinically indicated. Doses up to 240 mg daily have been administered.
  Indication	Dose	Frequency
  Short-Term Treatment of Erosive Esophagitis Associated With GERD
  Adults	40 mg	Once daily for up to 8 weeks*
  Children (5 years and older)≥ 15 kg to <40 kg≥ 40 kg	20 mg40 mg	Once daily for up to 8 weeks
  Maintenance of Healing of Erosive Esophagitis
  Adults	40 mg	Once daily†
  Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome
  Adults	40 mg	Twice daily‡

  Directions for method of administration for each dosage form are presented in Table 2.

  Table 2: Administration Instructions

  Formulation	Route	Instructions*
  *Patients should be cautioned that pantoprazole sodium delayed-release tablets should not be split, chewed, or crushed.
  Delayed-release Tablets	Oral	Swallowed whole, with or without food

  
  

  Pantoprazole sodium delayed-release tablets should be swallowed whole, with or without food in the stomach. If patients are unable to swallow a 40 mg tablet, two 20 mg tablets may be taken. Concomitant administration of antacids does not affect the absorption of pantoprazole sodium delayed-release tablets.

DOSAGE FORMS & STRENGTHS SECTION

• 40 mg, yellow round biconvex tablets imprinted with ‘124’ (black ink) on one side
• 20 mg, yellow round biconvex tablets imprinted with ‘144’ (black ink) on one side

CONTRAINDICATIONS SECTION

Pantoprazole sodium delayed-release tablets are contraindicated in patients with known hypersensitivity to any component of the formulation or any substituted benzimidazole. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria [see Adverse Reactions (6)].

WARNINGS AND PRECAUTIONS SECTION

• 5.1 Concurrent Gastric Malignancy
  

  Symptomatic response to therapy with pantoprazole does not preclude the presence of gastric malignancy.

  
  

  Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-term with pantoprazole, particularly in patients who were H. pylori positive.

  5.3 Acute Interstitial Nephritis

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

  
  

  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.

  
  

  Published observational studies suggest that PPI therapy like pantoprazole 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.

  
  

  Several published observational studies suggest that proton pump inhibitor (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) and Adverse Reactions (6.2)].

  
  

  Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, 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)].

  
  

  Due to the chronic nature of GERD, there may be a potential for prolonged administration of pantoprazole. 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)].

  
  

  See Drug Interactions (7.5).

  
  

  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 (7.6)].

ADVERSE REACTIONS SECTION

• 6.1 Clinical Trial Experience
  

  Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
  Adults Safety in nine randomized comparative U.S. clinical trials in patients with GERD included 1,473 patients on oral pantoprazole (20 mg or 40 mg), 299 patients on an H2-receptor antagonist, 46 patients on another proton pump inhibitor, and 82 patients on placebo. The most frequently occurring adverse reactions are listed in Table 3.

  Table 3: Adverse Reactions Reported in Clinical Trials of Adult Patients with GERD at a Frequency of > 2%

  	Pantoprazole (n=1,473)%	Comparators(n=345)%	Placebo(n=82)%
  Headache	12.2	12.8	8.5
  Diarrhea	8.8	9.6	4.9
  Nausea	7	5.2	9.8
  Abdominal pain	6.2	4.1	6.1
  Vomiting	4.3	3.5	2.4
  Flatulence	3.9	2.9	3.7
  Dizziness	3	2.9	1.2
  Arthralgia	2.8	1.4	1.2

  
  

  Additional adverse reactions that were reported for pantoprazole in clinical trials with a frequency of ≤ 2% are listed below by body system:
  Body as a Whole: allergic reaction, pyrexia, photosensitivity reaction, facial edema
  Gastrointestinal: constipation, dry mouth, hepatitis
  Hematologic: leukopenia, thrombocytopenia
  Metabolic/Nutritional: elevated CK (creatine kinase), generalized edema, elevated triglycerides, liver enzymes elevated
  Musculoskeletal: myalgia
  Nervous: depression, vertigo
  Skin and Appendages: urticaria, rash, pruritus
  Special Senses: blurred vision
  Pediatric Patients
  Safety of pantoprazole in the treatment of Erosive Esophagitis (EE) associated with GERD was evaluated in pediatric patients ages 1 year through 16 years in three clinical trials. Safety trials involved pediatric patients with EE; however, as EE is uncommon in the pediatric population, 249 pediatric patients with endoscopically-proven or symptomatic GERD were also evaluated. All adult adverse reactions to pantoprazole are considered relevant to pediatric patients. In patients ages 1 year through 16 years, the most commonly reported (> 4%) adverse reactions include: URI, headache, fever, diarrhea, vomiting, rash, and abdominal pain.
  For safety information in patients less than 1 year of age see Use in Specific Populations (8.4).
  Additional adverse reactions that were reported for pantoprazole in pediatric patients in clinical trials with a frequency of ≤ 4% are listed below by body system:
  Body as a Whole:allergic reaction, facial edema
  Gastrointestinal: constipation, flatulence, nausea
  Metabolic/Nutritional: elevated triglycerides, elevated liver enzymes, elevated CK (creatine kinase)
  Musculoskeletal: arthralgia, myalgia
  Nervous: dizziness, vertigo
  Skin and Appendages: urticaria
  The following adverse reactions seen in adults in clinical trials were not reported in pediatric patients in clinical trials, but are considered relevant to pediatric patients: photosensitivity reaction, dry mouth, hepatitis, thrombocytopenia, generalized edema, depression, pruritus, leukopenia, and blurred vision.

  Zollinger-Ellison Syndrome

  In clinical studies of Zollinger-Ellison Syndrome, adverse reactions reported in 35 patients taking pantoprazole 80 mg/day to 240 mg/day for up to 2 years were similar to those reported in adult patients with GERD.

  6.2 Postmarketing Experience

  The following adverse reactions have been identified during postapproval use of pantoprazole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  These adverse reactions are listed below by body system:

  General Disorders and Administration Conditions: asthenia, fatigue, malaise

  Hematologic: pancytopenia, agranulocytosis

  Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure

  Immune System Disorders: anaphylaxis (including anaphylactic shock)

  Infections and Infestations: Clostridium difficile associated diarrhea

  Investigations: weight changes

  Metabolism and Nutritional Disorders: hyponatremia, hypomagnesemia

  Musculoskeletal Disorders: rhabdomyolysis, bone fracture

  Nervous: ageusia, dysgeusia

  Psychiatric Disorders: hallucination, confusion, insomnia, somnolence

  Renal and Urinary Disorders: interstitial nephritis

  Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions (some fatal), including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN, some fatal), and angioedema (Quincke’s edema)