DESCRIPTION
id: cf9c40da-9243-4aae-9fec-42e454f96d74
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
The active ingredient in pantoprazole sodium delayed-release tablets is a substituted benzimidazole, sodium 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl] sulfinyl]-1
H
-benzimidazole sesquihydrate, a compound that inhibits gastric acid secretion. Its empirical formula is C16H14F2N3NaO4S x 1.5 H2O, with a molecular weight of 432.4. The structural formula is:
Pantoprazole sodium sesquihydrate is a white to off-white crystalline powder and is racemic. Pantoprazole has weakly basic and acidic properties. Pantoprazole sodium sesquihydrate is freely soluble in water, very slightly soluble in phosphate buffer at pH 7.4, and practically insoluble in n‑hexane.
The stability of the compound in aqueous solution is pH-dependent. The rate of degradation increases with decreasing pH. At ambient temperature, the degradation half-life is approximately 2.8 hours at pH 5.0 and approximately 220 hours at pH 7.8.
Pantoprazole sodium is supplied as a delayed-release tablet for oral administration, available in 2 strengths. Each delayed-release tablet contains 45.1 mg or 22.6 mg of pantoprazole sodium sesquihydrate (equivalent to 40 mg or 20 mg pantoprazole, respectively) with the following inactive ingredients: 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. Pantoprazole Sodium Delayed‑Release tablets (40 mg and 20 mg) complies with USP dissolution test 2.
CONTRAINDICATIONS
id: dfbecfa9-7e70-4de4-9d3d-b63fe95d7e95
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Pantoprazole sodium delayed-release tablets are contraindicated in patients with known hypersensitivity to any component of the formulation.
ADVERSE REACTIONS
id: 46f400be-9847-4b55-90e8-f59e35fca761
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
Worldwide, more than 11,100 patients have been treated with pantoprazole in clinical trials involving various dosages and duration of treatment. In general, pantoprazole has been well tolerated in both short-term and long-term trials.
In two U.S. controlled clinical trials involving pantoprazole sodium 10, 20, or 40 mg doses for up to 8 weeks, there were no dose-related effects on the incidence of adverse events. The following adverse events considered by investigators to be possibly, probably, or definitely related to drug occurred in 1% or more in the individual studies of GERD patients on therapy with pantoprazole sodium.
Most Frequent Adverse Events Reported as Drug Related in Short-term Domestic Trials
| |
––––––––––––––––––––––% Incidence––––––––––––––––– |
| |
Study 300-US |
Study 301-US |
| Study Event |
Pantoprazole sodium
(n = 521) |
Placebo
(n = 82) |
Pantoprazole sodium
(n = 161) |
Nizatidine (n = 82) |
Headache Diarrhea Flatulence Abdominal pain Rash
Eructation Insomnia Hyperglycemia |
6
4
2
1
<1
1
<1
1 |
6
1
2
2
0
1
2
0 |
9
6
4
4
2
0
1
<1 |
13
6
0
4
0
0
1
0 |
Note: Only adverse events with an incidence greater than or equal to the comparators are shown.
In international short-term, double-blind or open-label clinical trials involving 20 mg to 80 mg per day, the following adverse events were reported to occur in 1% or more of 2805 GERD patients receiving pantoprazole for up to 8 weeks.
Adverse Events in GERD Patients in Short-term International Trials
| |
–––––––––––––––––––––––––% Incidence––––––––––––––––––– |
| Study Event |
Pantoprazole Total
(N = 2805) |
Ranitidine 300 mg
(N = 594) |
Omeprazole
20 mg
(N = 474) |
Famotidine 40 mg
(N = 239) |
| Headache Diarrhea Abdominal pain |
2
2
1 |
3
2
1 |
2
2
<1 |
1
<1
<1 |
In two U.S. controlled clinical trials involving pantoprazole sodium 10, 20, or 40 mg doses for up to 12 months, the following adverse events considered by investigators to be possibly, probably, or definitely related to drug occurred in 1% or more of GERD patients on long-term therapy.
Most Frequent Adverse Events Reported as Drug Related in Long-term Domestic Trials
| |
–––––––––––––––––––% Incidence––––––––––––––– |
| Study Event |
Pantoprazole sodium
(n = 536) |
Ranitidine
(n = 185) |
Headache
Abdominal pain
Liver function tests abnormal
Nausea
Vomiting |
5
3
2
2
2 |
2
1
<1
2
2 |
| Note: Only adverse events with an incidence greater than or equal to the comparators are shown. |
In addition, in these short- and long-term domestic and international trials, the following treatment-emergent events, regardless of causality, occurred at a rate of ≥ 1% in pantoprazole-treated patients: anxiety, arthralgia, asthenia, back pain, bronchitis, chest pain, constipation, cough increased, dizziness, dyspepsia, dyspnea, flu syndrome, gastroenteritis, gastrointestinal disorder, hyperlipemia, hypertonia, infection, liver function tests abnormal, migraine, nausea, neck pain, pain, pharyngitis, rectal disorder, rhinitis, SGPT increased, sinusitis, upper respiratory tract infection, urinary frequency, urinary tract infection, and vomiting.
Additional treatment-emergent adverse experiences occurring in < 1% of pantoprazole-treated patients from these trials are listed below by body system. In most instances the relationship to pantoprazole was unclear.
BODY AS A WHOLE: abscess, allergic reaction, chills, cyst, face edema, fever, generalized edema, heat stroke, hernia, laboratory test abnormal, malaise, moniliasis, neoplasm, non-specified drug reaction, photosensitivity reaction.
CARDIOVASCULAR SYSTEM: abnormal electrocardiogram, angina pectoris, arrhythmia, atrial fibrillation/flutter, cardiovascular disorder, chest pain substernal, congestive heart failure, hemorrhage, hypertension, hypotension, myocardial infarction, myocardial ischemia, palpitation, retinal vascular disorder, syncope, tachycardia, thrombophlebitis, thrombosis, vasodilatation.
DIGESTIVE SYSTEM: anorexia, aphthous stomatitis, cardiospasm, colitis, dry mouth, duodenitis, dysphagia, enteritis, esophageal hemorrhage, esophagitis, gastrointestinal carcinoma, gastrointestinal hemorrhage, gastrointestinal moniliasis, gingivitis, glossitis, halitosis, hematemesis, increased appetite, melena, mouth ulceration, oral moniliasis, periodontal abscess, periodontitis, rectal hemorrhage, stomach ulcer, stomatitis, stools abnormal, tongue discoloration, ulcerative colitis.
ENDOCRINE SYSTEM: diabetes mellitus, glycosuria, goiter.
HEPATO-BILIARY SYSTEM: biliary pain, hyperbilirubinemia, cholecystitis, cholelithiasis, cholestatic jaundice, hepatitis, alkaline phosphatase increased, gamma glutamyl transpeptidase increased, SGOT increased.
HEMIC AND LYMPHATIC SYSTEM: anemia, ecchymosis, eosinophilia, hypochromic anemia, iron deficiency anemia, leukocytosis, leukopenia, thrombocytopenia.
METABOLIC AND NUTRITIONAL: dehydration, edema, gout, peripheral edema, thirst, weight gain, weight loss.
MUSCULOSKELETAL SYSTEM: arthritis, arthrosis, bone disorder, bone pain, bursitis, joint disorder, leg cramps, neck rigidity, myalgia, tenosynovitis.
NERVOUS SYSTEM: abnormal dreams, confusion, convulsion, depression, dry mouth, dysarthria, emotional lability, hallucinations, hyperkinesia, hypesthesia, libido decreased, nervousness, neuralgia, neuritis, neuropathy, paresthesia, reflexes decreased, sleep disorder, somnolence, thinking abnormal, tremor, vertigo.
RESPIRATORY SYSTEM: asthma, epistaxis, hiccup, laryngitis, lung disorder, pneumonia, voice alteration.
SKIN AND APPENDAGES: acne, alopecia, contact dermatitis, dry skin, eczema, fungal dermatitis, hemorrhage, herpes simplex, herpes zoster, lichenoid dermatitis, maculopapular rash, pruritus, skin disorder, skin ulcer, sweating, urticaria.
SPECIAL SENSES: abnormal vision, amblyopia, cataract specified, deafness, diplopia, ear pain, extraocular palsy, glaucoma, otitis externa, taste perversion, tinnitus.
UROGENITAL SYSTEM: albuminuria, balanitis, breast pain, cystitis, dysmenorrhea, dysuria, epididymitis, hematuria, impotence, kidney calculus, kidney pain, nocturia, prostatic disorder, pyelonephritis, scrotal edema, urethral pain, urethritis, urinary tract disorder, urination impaired, vaginitis.
In an open-label US clinical trial conducted in 35 patients with pathological hypersecretory conditions treated with pantoprazole sodium for up to 27 months, the adverse events reported were consistent with the safety profile of the drug in other populations.
OVERDOSAGE
id: 098d8523-5e2b-4e59-a6cc-f53496449029
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
Experience in patients taking very high doses of pantoprazole is limited. There have been spontaneous reports of overdosage with pantoprazole, including a suicide in which pantoprazole 560 mg and undetermined amounts of chloroquine and zopiclone were also ingested. There have also been spontaneous reports of patients taking similar amounts of pantoprazole (400 mg and 600 mg) with no adverse effects.
Pantoprazole is not removed by hemodialysis. In case of overdosage, treatment should be symptomatic and supportive.
Single oral doses of pantoprazole at 709 mg/kg, 798 mg/kg, and 887 mg/kg were lethal to mice, rats, and dogs, respectively. The symptoms of acute toxicity were hypoactivity, ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex, and tremor.
HOW SUPPLIED
id: 3b27e282-d483-4419-8927-b11b68375576
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Pantoprazole sodium delayed-release tablets are supplied as 40 mg yellow oval biconvex delayed‑release tablets imprinted with PROTONIX (brown ink) on one side.
They are available as follows:
- NDC 67046-535-30 blister of 30
PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 40 MG LABEL
id: 7db77b1b-2ee8-4b55-8467-bc9e7202c861
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
esiLEDERLE™
NDC 67046-535-30
Pantoprazole Sodium
Delayed-Release Tablets
Equivalent to 40 mg pantoprazole
40 mg
Rx Only
30 Tablets
