Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1797
Predicate | Object |
---|---|
rdf:type | |
rdfs:label |
Pantoprazole Sodium (Tablet, Delayed Release)
|
dailymed-instance:dosage |
Treatment of Erosive Esophagitis: The recommended
adult oral dose is 40 mg given once daily for up to 8 weeks.For those patients who have not healed after 8 weeks of treatment,
an additional 8-week course of pantoprazole sodium may be considered
(see INDICATIONS AND
USAGE).<br/>Maintenance of Healing of Erosive Esophagitis: The recommended
adult oral dose is one pantoprazole sodium 40 mg delayed-release
tablet, taken daily .<br/>Pathological Hypersecretory Conditions Including Zollinger-Ellison
Syndrome: The dosage of pantoprazole
sodium in patients with pathological hypersecretory conditions varies
with the individual patient. The recommended adult starting dose is
40 mg twice daily. 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. Some patients
have been treated continuouslywith pantoprazole sodium for more than
2 years. No dosage
adjustment is necessary in patients with renal impairment, hepatic
impairment, or for elderly patients. Doses higher than 40 mg/day
have not been studied in hepatically-impaired patients. No dosage
adjustment is necessary in patients undergoing hemodialysis. 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. Patients should be cautioned that pantoprazole sodium delayed-release
tablets should not be split, chewed or crushed.
|
dailymed-instance:descripti... |
The active ingredient in
pantoprazole sodium delayed-release tablets is a substituted benzimidazole,
sodium 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]
sulfinyl]-1H-benzimidazole
sesquihydrate, a compound that inhibits gastric acid secretion. Its
empirical formula is CHFNNaOS x 1.5 HO, 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.
|
dailymed-instance:clinicalP... |
Pharmacokinetics: Pantoprazole sodium
is prepared as an enteric-coated tablet so that absorption of pantoprazole
begins only after the tablet leaves the stomach. Peak serum concentration
(C) and area under the serum concentration time curve
(AUC) increase in a manner proportional to oral and intravenous doses
from 10 mg to 80 mg. Pantoprazole does not accumulate and
its pharmacokinetics are unaltered with multiple daily dosing. Following
oral or intravenous administration, the serum concentration of pantoprazole
declines biexponentially with a terminal elimination half-life of
approximately one hour. In extensive metabolizers (see CLINICAL PHARMACOLOGY, Pharmacokinetics,
Metabolism) with normal liver function receiving
an oral dose of the enteric-coated 40 mg pantoprazole tablet,
the peak concentration (C) is 2.5��g/mL,
the time to reach the peak concentration (t) is 2.5 h
and the total area under the plasma concentration versus time curve
(AUC) is 4.8��g��hr/mL. When pantoprazole is given
with food, its tis highly variable and may increase
significantly. Following intravenous administration of pantoprazole
to extensive metabolizers, its total clearance is 7.6-14.0 L/h
and its apparent volume of distribution is 11.0-23.6 L.<br/>Absorption: The absorption
of pantoprazole is rapid, with a Cof 2.5��g/mL
that occurs approximately 2.5 hours after administration of a single
or multiple oral 40-mg doses of pantoprazole sodium delayed-release
tablets. Pantoprazole is well absorbed; it undergoes little first-pass
metabolism resulting in an absolute bioavailability of approximately
77%. Pantoprazole absorption is not affected by concomitant administration
of antacids. Administration of pantoprazole with food may delay its
absorption up to 2 hours or longer; however, theCand
the extent of pantoprazole absorption (AUC) are not altered. Thus,
pantoprazole may be taken without regard to timing of meals.<br/>Distribution: The apparent
volume of distribution of pantoprazole is approximately 11.0-23.6
L, distributing mainly in extracellular fluid. The serum protein binding
of pantoprazole is about 98%, primarily to albumin.<br/>Metabolism: Pantoprazole
is extensively metabolized in the liver through the cytochrome P450
(CYP) system. Pantoprazole metabolism is independent of the route
of administration (intravenous or oral). The main metabolic pathway
is demethylation, by CYP2C19, with subsequent sulfation; other metabolic
pathways include oxidation by CYP3A4. There is no evidence that any
of the pantoprazole metabolites have significant pharmacologic activity.
CYP2C19 displays a known genetic polymorphism due to its deficiency
in some sub-populations (eg, 3% of Caucasians and African-Americans
and 17%-23% of Asians). Although these sub-populations of slow pantoprazole
metabolizers have elimination half-life values of 3.5 to 10.0 hours,
they still have minimal accumulation (���23%) with once daily
dosing.<br/>Elimination: After a
single oral or intravenous dose ofC-labeled pantoprazole
to healthy, normal metabolizer volunteers, approximately 71% of the
dose was excreted in the urine with 18% excreted in the feces
through biliary excretion. There was no renal excretion of unchanged
pantoprazole.<br/>Special
Populations:<br/>Drug-Drug Interactions: Pantoprazole is
metabolized mainly by CYP2C19 and to minor extents by CYPs 3A4,
2D6, and 2C9. In in vivo drug-drug interaction studies with CYP2C19
substrates (diazepam [also a CYP3A4 substrate] and phenytoin [also
a CYP3A4 inducer]), nifedipine, midazolam, and clarithromycin (CYP3A4
substrates), metoprolol (a CYP2D6 substrate), diclofenac, naproxen
and piroxicam (CYP2C9 substrates), and theophylline (a CYP1A2 substrate)
in healthy subjects, the pharmacokinetics of pantoprazole were not
significantly altered. It is, therefore, expected that other drugs
metabolized by CYPs 2C19, 3A4, 2D6, 2C9, and 1A2 would notsignificantly
affect the pharmacokinetics of pantoprazole. In vivo studies also
suggest that pantoprazole does not significantly affect the kinetics
of other drugs (cisapride, theophylline, diazepam [and its active
metabolite, desmethyldiazepam], phenytoin, warfarin, metoprolol, nifedipine,
carbamazepine, midazolam, clarithromycin, naproxen, piroxicam, and
oral contraceptives [levonorgestrel/ethinyl estradiol]) metabolized
by CYPs 2C19, 3A4, 2C9, 2D6, and 1A2. Therefore, it is expected
that pantoprazole would not significantly affect the pharmacokinetics
of other drugs metabolized by these isozymes. Dosage adjustment of
such drugs is not necessary when they are coadministered with pantoprazole.
In other in vivo studies, digoxin, ethanol, glyburide, antipyrine,
caffeine, metronidazole, and amoxicillin had no clinically relevant
interactions with pantoprazole. Although no significant drug-drug
interactions have been observed in clinical studies, the potential
for significant drug-drug interactions with more than once daily dosing
with high doses of pantoprazole has not been studied in poor metabolizers
or individuals who are hepatically impaired.<br/>Pharmacodynamics:<br/>Mechanism
of Action: Pantoprazole
is a proton pump inhibitor (PPI) that suppresses the final step in
gastric acid production by covalently binding to the (H,K)-ATPase enzyme system at the secretory surface of
the gastric parietal cell. This effect leads to inhibition of both
basal and stimulated gastric acid secretion irrespective of the stimulus.
The binding to the (H,K)-ATPase results in
a duration of antisecretory effect that persists longer than 24 hours
for all doses tested.<br/>Antisecretory
Activity: Under maximal
acid stimulatory conditions using pentagastrin, a dose-dependent decrease
in gastric acid output occurs after a single dose of oral (20-80 mg)
or a single dose of intravenous (20-120 mg) pantoprazole in healthy
volunteers. Pantoprazole given once daily results in increasing inhibition
of gastric acid secretion. Following the initial oral dose of 40 mg
pantoprazole, a 51% mean inhibition was achieved by 2.5 hours. With
once a day dosing for 7 days the mean inhibition was increased
to 85%. Pantoprazole suppressed acid secretion in excess of 95% in
half of the subjects. Acid secretion had returned to normal within
a week after the last dose of pantoprazole; there was no evidence
of rebound hypersecretion. In a series of dose-response studies pantoprazole, at oral doses
ranging from 20 to 120 mg, caused dose-related increases in median
basal gastric pH and in the percent of time gastric pH was>3 and>4. Treatment with 40 mg of pantoprazole produced optimal increases
in gastric pH which were significantly greater than the 20-mg dose.
Doses higher than 40 mg (60, 80, 120 mg)
did not result in further significant increases in median gastric
pH. The effects of pantoprazole on median pH from one double-blind
crossover study are shown below.<br/>Serum
Gastrin Effects: Fasting
serum gastrin levels were assessed in two double-blind studies of
the acute healing of erosive esophagitis (EE) in which 682 patients
with gastroesophageal reflux disease (GERD) received 10, 20, or
40 mg of pantoprazole sodium for up to 8 weeks. At 4 weeks of
treatment there was an increase in mean gastrin levels of 7%, 35%,
and 72% over pretreatment values in the 10, 20, and 40 mg
treatment groups, respectively. A similar increase in serum gastrin
levels was noted at the 8 week visit with mean increases of 3%, 26%,
and 84% for the three pantoprazole dose groups. Median serum gastrin
levels remained within normal limits during maintenance therapy with
pantoprazole sodium delayed-release tablets. In long-term international studies involving over 800 patients, a
2- to 3-fold mean increase from the pretreatment fasting serum gastrin
level was observed in the initial months of treatment with pantoprazole
at doses of 40 mg per day during GERD maintenance studies and
40 mg or higher per day in patients with refractory GERD. Fasting
serum gastrin levels generally remained at approximately 2 to 3 times
baseline for up to 4 years of periodic follow-up in clinical trials. Following healing
of gastric or duodenal ulcers with pantoprazole treatment, elevated
gastrin levels return to normal by at least 3 months.<br/>Enterochromaffin-Like
(ECL) Cell Effects: In 39 patients
treated with oral pantoprazole 40 mg to 240 mg
daily (majority receiving 40 mg to 80 mg) for
up to 5 years, there was a moderate increase in ECL-cell density starting
after the first year of use which appeared to plateau after 4 years. In a nonclinical
study in Sprague-Dawley rats, lifetime exposure (24 months) to pantoprazole
at doses of 0.5 to 200 mg/kg/day resulted in dose-related increases
in gastric ECL-cell proliferation and gastric neuroendocrine (NE)-cell
tumors. Gastric NE-cell tumors in rats may result from chronic elevation
of serum gastrin concentrations. The high density of ECL cells
in the rat stomach makes this species highly susceptible to the proliferative
effects of elevated gastrin concentrations produced by proton pump
inhibitors. However, there were no observed elevations in serum gastrin
following the administration of pantoprazole at a dose of 0.5 mg/kg/day.
In a separate study, a gastric NE-cell tumor without concomitant ECL-cell
proliferative changes was observed in 1 female rat following 12 months
of dosing with pantoprazole at 5 mg/kg/day and a 9 month off-dose
recovery (see PRECAUTIONS,
Carcinogenesis, Mutagenesis, Impairment of Fertility).<br/>Other
Effects: No clinically
relevant effects of pantoprazole on cardiovascular, respiratory, ophthalmic,
or central nervous system function have been detected. In a clinical
pharmacology study, pantoprazole 40 mg given once daily for 2
weeks had no effect on the levels of the following hormones: cortisol,
testosterone, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating
hormone (TSH), thyronine-binding protein, parathyroid hormone, insulin,
glucagon, renin, aldosterone, follicle-stimulating hormone, luteinizing
hormone, prolactin, and growth hormone. In a 1-year study of GERD patients treated with pantoprazole 40 mg
or 20 mg, there were no changes from baseline in overall levels
of T3, T4, and TSH.<br/>Clinical Studies: Pantoprazole sodium
delayed-release tablets were used in all clinical trials.<br/>Erosive Esophagitis (EE) Associated with Gastroesophageal Reflux
Disease (GERD): A U.S. multicenter
double-blind, placebo-controlled study of pantoprazole sodium 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 were asfollows: In this study,
all pantoprazole sodium 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
pantoprazole sodium treatment groups. The 40-mg dose of pantoprazole
sodium resulted in healing rates significantly greater than those
found with either the 20- or 10-mg dose. A significantly greater proportion of patients taking pantoprazole
sodium 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 pantoprazole
sodium consumed significantly fewer antacid tablets per day than those
taking placebo. Pantoprazole sodium 40 mg and 20 mg once daily were also
compared with nizatidine 150 mg twice daily in a U.S. 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) were as follows: Once daily treatment
with pantoprazole sodium 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 pantoprazole
sodium 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 pantoprazole sodium consumed significantly
fewer antacid tablets per day than those taking nizatidine.<br/>Long-Term Maintenance of Healing of Erosive Esophagitis: Two independent,
multicenter, randomized, double-blind, comparator-controlled trials
of identical design were conducted in GERD patients with endoscopically-confirmed
healed erosive esophagitis to demonstrate efficacy of pantoprazole
sodium in long-term maintenance of healing. The two U.S. studies enrolled
386 and 404 patients, respectively, to receive either 10 mg,
20 mg, or 40 mg of pantoprazole sodium delayed-release tablets
once daily or 150 mg of ranitidine twice daily. As demonstrated
in the table below, pantoprazole sodium 40 mg and 20 mg
were significantly superior to ranitidine at every time point with
respect to the maintenance of healing. In addition, pantoprazole sodium
40 mg was superior to all other treatments studied. Pantoprazole sodium
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. Pantoprazole sodium 20 mg, administered once
daily, was also effective in reducing episodes of daytime and nighttime
heartburn in one trial.<br/>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, pantoprazole sodium 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
. Pantoprazole sodium was well tolerated at these dose
levels for prolonged periods (greater than 2 years in some patients).
|
dailymed-instance:activeIng... | |
dailymed-instance:contraind... |
Pantoprazole sodium delayed-release
tablets are contraindicated in patients with known hypersensitivity
to any component of the formulation.
|
dailymed-instance:supply |
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: Pantoprazole sodium delayed���release tablets are supplied as
20 mg yellow oval biconvex delayed���release tablets imprinted
with P20 (brown ink) on one side. They are available
as follows:<br/>Storage: Store pantoprazole
sodium delayed-release tablets at 20��-25��C (68��-77��F);
excursions permitted to 15��-30��C (59��-86��F).
[See USP Controlled Room Temperature.] United States Patent Numbers: 4,758,579; 5,997,903. Packaged
byWyeth Pharmaceuticals CompanyGuayama, PR 00784for
Marketing byesiLederle Division of Wyeth,under license fromNycomed GmbHD78467 Konstanz, Germany W10525C004ET01Rev 01/08
|
dailymed-instance:activeMoi... | |
dailymed-instance:inactiveI... |
dailymed-ingredient:Calcium_Stearate,
dailymed-ingredient:Crospovidone,
dailymed-ingredient:Hypromellose,
dailymed-ingredient:Iron_Oxide,
dailymed-ingredient:Mannitol,
dailymed-ingredient:Methacrylic_Acid_Copolymer,
dailymed-ingredient:Polysorbate_80,
dailymed-ingredient:Povidone,
dailymed-ingredient:Propylene_Glycol,
dailymed-ingredient:Sodium_Carbonate,
dailymed-ingredient:Sodium_Lauryl_Sulfate,
dailymed-ingredient:Titanium_Dioxide,
dailymed-ingredient:Triethyl_Citrate
|
dailymed-instance:precautio... |
General: Symptomatic response
to therapy with pantoprazole does not preclude the presence of gastric
malignancy. Owing
to the chronic nature of erosive esophagitis, 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. Generally, daily treatment with any acid-suppressing medications
over a long period of time (eg, 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 possibility should
be considered if clinical symptoms consistent with cyanocobalamin
deficiency are observed. 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.<br/>Information for Patients: Patients should
be cautioned that pantoprazole sodium delayed-release tablets SHOULD
NOT BE SPLIT, CRUSHED OR CHEWED. The tablets should be swallowed whole,
with or without food in the stomach. Concomitant administration of
antacids does not affect the absorption of pantoprazole.<br/>Drug Interactions: Pantoprazole is
metabolized through the cytochrome P450 system, primarily the CYP2C19
and CYP3A4 isozymes, and subsequently undergoes Phase II conjugation
(see CLINICAL PHARMACOLOGY,
Drug-Drug Interactions). Based on studies evaluating possible interactions of pantoprazole
with other drugs, no dosage adjustment is needed with concomitant
use of the following: theophylline, cisapride, antipyrine, caffeine,
carbamazepine, diazepam (and its active metabolite, desmethyldiazepam),
diclofenac, naproxen, piroxicam, digoxin, ethanol, glyburide, an oral
contraceptive (levonorgestrel/ethinyl estradiol), metoprolol, nifedipine,
phenytoin, warfarin (see below), midazolam, clarithromycin, metronidazole,
or amoxicillin. Clinically relevant interactions of pantoprazole with
other drugs with the same metabolic pathways are not expected. Therefore,
when coadministered with pantoprazole, adjustment of the dosage of
pantoprazole or of such drugs may not be necessary. There was also
no interaction with concomitantly administered antacids. There have
been postmarketing reports of increased INR and prothrombin time in
patients receiving proton pump inhibitors, including pantoprazole,
and warfarin concomitantly. Increases in INR and prothrombin time
may lead to abnormal bleeding and even death. Patients treated with
proton pump inhibitors and warfarin concomitantly should be monitored
for increases in INR and prothrombin time. Concomitant use of atazanavir and proton pump inhibitors is not recommended.
Coadministration of atazanavir with proton pump inhibitors is expected
to substantially decrease atazanavir plasma concentrations and thereby
reduce its therapeutic effect. Because of profound
and long lasting inhibition of gastric acid secretion, pantoprazole
may interfere with absorption of drugs where gastric pH is an important
determinant of their bioavailability (eg, ketoconazole, ampicillin
esters, and iron salts).<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: In a 24-month carcinogenicity
study, Sprague-Dawley rats were treated orally with doses of 0.5 to 200 mg/kg/day,
about 0.1 to 40 times the exposure on a body surface area basis of
a 50-kg person dosed at 40 mg/day. In the gastric fundus, treatment
at 0.5 to 200 mg/kg/day produced enterochromaffin-like
(ECL) cell hyperplasia and benign and malignant neuroendocrine cell
tumors in a dose-related manner. In theforestomach, treatment at
50 and 200 mg/kg/day (about 10 and 40 times the recommended human
dose on a body surface area basis) produced benign squamous cell papillomas
and malignant squamous cell carcinomas. Rare gastrointestinal tumors
associated with pantoprazole treatment included an adenocarcinoma
of the duodenum at 50 mg/kg/day, and benign polyps and adenocarcinomas
of the gastric fundus at 200 mg/kg/day. In the liver, treatment
at 0.5 to 200 mg/kg/day produced dose-related increases
in the incidencesof hepatocellular adenomas and carcinomas. In the
thyroid gland, treatment at 200 mg/kg/day produced increased
incidences of follicular cell adenomas and carcinomas for both male
and female rats. Sporadic occurrences of hepatocellular adenomas and a hepatocellular
carcinoma were observed in Sprague-Dawley rats exposed to pantoprazole
in 6-month and 12-month toxicity studies. In a 24-month carcinogenicity study, Fischer 344 rats were treated
orally with doses of 5 to 50 mg/kg/day, approximately
1 to 10 times the recommended human dose based on body surface area.
In the gastric fundus, treatment at 5 to 50 mg/kg/day produced
enterochromaffin-like (ECL) cell hyperplasia and benign and malignant
neuroendocrine cell tumors. Dose selection for this study may not
have been adequate to comprehensively evaluate the carcinogenic potential
of pantoprazole. In a 24-month carcinogenicity study, B6C3F1 mice were treated orally
with doses of 5 to 150 mg/kg/day, 0.5 to 15 times the
recommended human dose based on body surface area. In the liver, treatment
at 150 mg/kg/day produced increased incidences of hepatocellular
adenomas and carcinomas in female mice. Treatment at 5 to 150 mg/kg/day
also produced gastric fundic ECL cell hyperplasia. A 26-week p53 +/- transgenic mouse carcinogenicity study was not
positive. Pantoprazole was positive in the in vitro human lymphocyte chromosomal
aberration assays, in one of two mouse micronucleus tests for clastogenic
effects, and in the in vitro Chinese hamster ovarian cell/HGPRT forward
mutation assay for mutagenic effects. Equivocal results were observed
in the in vivo rat liver DNA covalent binding assay. Pantoprazole
was negative in the in vitro Ames mutation assay, the in vitro unscheduled
DNA synthesis (UDS) assay with rat hepatocytes, the in vitro AS52/GPT
mammalian cell-forward gene mutation assay, the in vitro thymidine
kinase mutation test with mouse lymphoma L5178Ycells, and the in
vivo rat bone marrow cell chromosomal aberration assay. Pantoprazole at oral doses
up to 500 mg/kg/day in male rats (98 times the recommended human
dose based on body surface area) and 450 mg/kg/day in female
rats (88 times the recommended human dose based on body surface area)
was found to have no effect on fertility and reproductive performance.<br/>Pregnancy:<br/>Teratogenic
Effects:<br/>Nursing Mothers: Pantoprazole and
its metabolites are excreted in the milk of rats. Pantoprazole excretion
in human milk has been detected in a study of a single nursing mother
after a single 40 mg oral dose. The clinical relevance of this finding
is not known. Many drugs which are excreted in human milk have a potential
for serious adverse reactions in nursing infants. Based on the potential
for tumorigenicity shown for pantoprazole in rodent carcinogenicitystudies, a decision should be made whether to discontinue nursing
or to discontinue the drug, taking into account the benefit of the
drug to the mother.<br/>Pediatric Use: Safety and effectiveness
in pediatric patients have not been established.<br/>Use in Women: Erosive esophagitis
healing rates in the 221 women treated with pantoprazole sodium delayed-release
tablets in U.S. clinical trials were similar to those found in men.
In the 122 women treated long-term with pantoprazole sodium 40 mg
or 20 mg, healing was maintained at a rate similar to that in
men. The incidence rates of adverse events were also similar for men
and women.<br/>Use in Elderly: In short-term U.S.
clinical trials, erosive esophagitis healing rates in the 107 elderly
patients (���65 years old) treated with pantoprazole
sodium were similar to those found in patients under the age of 65.
The incidence rates of adverse events and laboratory abnormalities
in patients aged 65 years and older were similar to those associated
with patients younger than 65 years of age.<br/>Laboratory Tests: There have been
reports of false-positive urine screening tests for tetrahydrocannabinol
(THC) in patients receiving most proton pump inhibitors, including
pantoprazole. An alternative confirmatory method should be considered
to verify positive results.
|
dailymed-instance:overdosag... |
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.
|
dailymed-instance:genericMe... |
pantoprazole sodium
|
dailymed-instance:fullName |
Pantoprazole Sodium (Tablet, Delayed Release)
|
dailymed-instance:adverseRe... |
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. 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. 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. 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, periodontalabscess, 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.<br/>Postmarketing Reports: There have been
spontaneous reports of adverse events with the postmarketing use of
pantoprazole. These reports include the following: BODY AS A WHOLE: anaphylaxis (including anaphylactic shock), angioedema
(Quincke's edema). DIGESTIVE SYSTEM: increased salivation, nausea, pancreatitis. HEMIC AND LYMPHATIC SYSTEM:
pancytopenia. HEPATO-BILIARY SYSTEM: hepatocellular damage leading to jaundice
and hepatic failure. MUSCULOSKELETAL SYSTEM: elevated CPK (creatine phosphokinase), rhabdomyolysis. NERVOUS SYSTEM: confusion,
hypokinesia, speech disorder, vertigo. SKIN AND APPENDAGES: severe dermatologic reactions, including erythema
multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis
(TEN, some fatal). SPECIAL SENSES: anterior ischemic optic neuropathy, blurred vision,
tinnitus. UROGENITAL SYSTEM: interstitial nephritis.<br/>Laboratory Values: In two U.S. controlled,
short-term trials in patients with erosive esophagitis associated
with GERD, 0.4% of the patients on pantoprazole sodium 40 mg
experienced SGPT elevations of greater than three times the upper
limit of normal at the final treatment visit. In two U.S. controlled,
long-term trials in patients with erosive esophagitis associated with
GERD, none of 178 patients (0%) on pantoprazole sodium 40 mg
and two of 181 patients (1.1%) on pantoprazole sodium 20 mg experienced
significant transaminase elevations at 12 months (or earlier if a
patient discontinued prematurely). Significant elevations of SGOT
or SGPT were defined as values at least three times the upper limit
of normal that were non-sporadic and had no clear alternative explanation.
The following changes in laboratory parameters were reported as adverse
events: creatinine increased, hypercholesterolemia, and hyperuricemia.
|
dailymed-instance:indicatio... |
Short-Term Treatment of Erosive Esophagitis Associated With
Gastroesophageal Reflux Disease (GERD): Pantoprazole sodium
delayed-release tablets are indicated for the short-term treatment
(up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis.
For those patients who have not healed after 8 weeks of treatment,
an additional 8-week course of pantoprazole sodium may be considered.<br/>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 patients with gastroesophageal reflux
disease (GERD). Controlled studies did not extend beyond 12 months.<br/>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.
|
dailymed-instance:represent... | |
dailymed-instance:routeOfAd... | |
dailymed-instance:name |
Pantoprazole Sodium
|