PANTOPRAZOLE SODIUM- pantoprazole sodium tablet, delayed release
NuCare Pharmaceuticals, Inc.
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.
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.
* 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.
* * 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.
*** Controlled studies did not extend beyond 12 months
|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 mg 40 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**|
|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.
- 20 mg, white to pale yellow colored, oval shape, biconvex, enteric-coated tablets, plain on one side and “96” printed with brown ink on the other side.
- 40 mg, white to pale yellow colored, oval shape, biconvex, enteric-coated tablets, plain on one side and “1097” printed with brown ink on the other side.
Pantoprazole sodium is 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)].
In adults, symptomatic response to therapy with pantoprazole 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.
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 if acute interstitial nephritis develops [see Contraindications (4)].
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)].
Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including pantoprazole. 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 pantoprazole, 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.
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.
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) ].
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)].
- Acute Interstitial Nephritis [see Warnings and Precautions (5.2)]
- Clostridium difficile- Associated Diarrhea [see Warnings and Precautions (5.3)]
- Bone Fracture [see Warnings and Precautions (5.4)]
- Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.5)]
- Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.6)]
- Hypomagnesemia [see Warnings and Precautions (5.7)]
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.
Safety in nine randomized comparative US clinical trials in patients with GERD included 1,473 patients on oral pantoprazole (20 mg or 40 mg), 299 patients on an H 2 -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.
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
Nervous: depression, vertigo
Skin and Appendages: urticaria, rash, pruritus
Special Senses: blurred vision
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.
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.
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