|
|
|||
|
|||
|
|
|||
|
fda approved arthrotec |
|||
|
|
|||
|
|||
 
|
|||
|
|
|||
|
fda approved arthrotec Manufacturer: Searle (diclofenac sodium and misoprostol) tablets
PATIENTS MUST BE ADVISED OF THE ABORTIFACIENT PROPERTY AND WARNED NOT TO GIVETHE DRUG TO OTHERS fda approved arthrotec. UTERINE RUPTURE HAS BEEN REPORTED WHEN MISOPROSTOL WAS ADMINISTERED INTRAVAGINALLYIN PREGNANT WOMEN TO INDUCE LABOR OR TO INDUCE ABORTION BEYOND THE FIRST TRIMESTEROF PREGNANCY fda approved arthrotec. UTERINE PERFORATION HAS BEEN REPORTED FOLLOWING ADMINISTRATION OF COMBINEDVAGINAL-AND-ORAL MISOPROSTOL IN PREGNANT WOMEN TO INDUCE ABORTION fda approved arthrotec. IN EACH OFTHESE REPORTED CASES, THE GESTATIONAL AGE OF THE PREGNANCIES WAS UNKNOWN fda approved arthrotec. ARTHROTEC should not be used in women of childbearing potential unless thepatient requires nonsteroidal anti-inflammatory drug (NSAID) therapy and isat high risk of developing gastric or duodenal ulceration or for developingcomplications from gastric or duodenal ulcers associated with the use of theNSAID fda approved arthrotec. (See WARNINGS ) fda approved arthrotec. In such patients, ARTHROTEC may be prescribed if thepatient:
Diclofenac sodium is a phenylacetic acid derivative that is a white to off-white,virtually odorless, crystalline powder fda approved arthrotec. Diclofenac sodium is freely solublein methanol, soluble in ethanol and practically insoluble in chloroform andin dilute acid fda approved arthrotec. Diclofenac sodium is sparingly soluble in water fda approved arthrotec. Its chemicalformula and name are: C 14 H 10 Cl 2 NO 2 Na [M.W fda approved arthrotec. = 318.14] 2-[ (2, 6-dichlorophenyl) amino] benzeneaceticacid, monosodium salt fda approved arthrotec. Misoprostol is a water-soluble, viscous liquid that contains approximatelyequal amounts of two diastereomers fda approved arthrotec. Its chemical formula and name are: C 22 H 38 O 5 [M.W fda approved arthrotec. = 382.54] (±)methyl 11(alpha), 16-dihydroxy-16-methyl-9-oxoprost-13E-en-1-oate fda approved arthrotec. Inactive ingredients in ARTHROTEC include: colloidal silicon dioxide; crospovidone;hydrogenated castor oil; hydroxypropyl methylcellulose; lactose; magnesium stearate;methacrylic acid copolymer; microcrystalline cellulose; povidone (polyvidone)K-30; sodium hydroxide; starch (corn); talc; triethyl citrate fda approved arthrotec.
Diclofenac sodium is completely absorbed from the GI tract after fasting, oraladministration fda approved arthrotec. The diclofenac sodium in ARTHROTEC is in a pharmaceutical formulationthat resists dissolution in the low pH of gastric fluid but allows a rapid releaseof drug in the higher pH environment of the duodenum fda approved arthrotec. Only 50% of the absorbeddose is systemically available due to first pass metabolism fda approved arthrotec. Peak plasma levelsare achieved in 2 hours (range 1-4 hours), and the area under the plasma concentrationcurve (AUC) is dose proportional within the range of 25 mg to 150 mg fda approved arthrotec. Peak plasmalevels are less than dose proportional and are approximately 1.5 and 2.0 mcg/mLfor 50 mg and 75 mg doses, respectively fda approved arthrotec. Plasma concentrations of diclofenac sodium decline from peak levels in a biexponentialfashion, with the terminal phase having a half-life of approximately 2 hours fda approved arthrotec. Clearance and volume of distribution are about 350 mL/min and 550 mL/kg, respectively fda approved arthrotec. More than 99% of diclofenac sodium is reversibly bound to human plasma albumin fda approved arthrotec. Diclofenac sodium is eliminated through metabolism and subsequent urinary andbiliary excretion of the glucuronide and the sulfate conjugates of the metabolites fda approved arthrotec. Approximately 65% of the dose is excreted in the urine and 35% in the bile fda approved arthrotec. Conjugates of unchanged diclofenac account for 5-10% of the dose excreted inthe urine and for less than 5% excreted in the bile fda approved arthrotec. Little or no unchangedunconjugated drug is excreted fda approved arthrotec. Conjugates of the principal metabolite accountfor 20-30% of the dose excreted in the urine and for 10-20% of the dose excretedin the bile fda approved arthrotec. Conjugates of three other metabolites together account for 10-20% of the doseexcreted in the urine and for small amounts excreted in the bile fda approved arthrotec. The eliminationhalf-life values for these metabolites are shorter than those for the parentdrug fda approved arthrotec. Urinary excretion of an additional metabolite (half-life = 80 hours) accountsfor only 1.4% of the oral dose fda approved arthrotec. The degree of accumulation of diclofenac metabolitesis unknown fda approved arthrotec. Some of the metabolites may have activity fda approved arthrotec. Pharmacodynamics and pharmacokinetics of misoprostol Misoprostol can increase bicarbonate and mucus production, but in humans thishas been shown at doses 200 mcg and above that are also antisecretory fda approved arthrotec. It istherefore not possible to tell whether the ability of misoprostol to preventgastric and duodenal ulcers is the result of its antisecretory effect, its mucosalprotective effect, or both fda approved arthrotec. In vitro studies on canine parietal cells using tritiated misoprostol acidas the ligand have led to the identification and characterization of specificprostaglandin receptors fda approved arthrotec. Receptor binding is saturable, reversible, and stereospecific fda approved arthrotec. The sites have a high affinity for misoprostol, for its acid metabolite, andfor other E type prostaglandins, but not for F or I prostaglandins and otherunrelated compounds, such as histamine or cimetidine fda approved arthrotec. Receptor-site affinityfor misoprostol correlates well with an indirect index of antisecretory activity fda approved arthrotec. It is likely that these specific receptors allow misoprostol taken with foodto be effective topically, despite the lower serum concentrations attained fda approved arthrotec. Misoprostol produces a moderate decrease in pepsin concentration during basalconditions, but not during histamine stimulation fda approved arthrotec. It has no significant effecton fasting or postprandial gastrin nor intrinsic factor output fda approved arthrotec. Effects on gastric acid secretion: Misoprostol, over the range of 50-200 mcg,inhibits basal and nocturnal gastric acid secretion, and acid secretion in responseto a variety of stimuli, including meals, histamine, pentagastrin, and coffee fda approved arthrotec. Activity is apparent 30 minutes after oral administration and persists for atleast 3 hours fda approved arthrotec. In general, the effects of 50 mcg were modest and shorter lived,and only the 200-mcg dose had substantial effects on nocturnal secretion oron histamine-and meal-stimulated secretion fda approved arthrotec. Orally administered misoprostol is rapidly and extensively absorbed, and itundergoes rapid metabolism to its biologically active metabolite, misoprostolacid fda approved arthrotec. Misoprostol acid in ARTHROTEC reaches a maximum plasma concentration inabout 20 minutes and is, thereafter, quickly eliminated with an eliminationt 1/2 of about 30 minutes fda approved arthrotec. There is high variability in plasma levels of misoprostolacid between and within studies, but mean values after single doses show a linearrelationship with dose of misoprostol over the range of 200 to 400 mcg fda approved arthrotec. No accumulationof misoprostol acid was found in multiple-dose studies, and plasma steady statewas achieved within 2 days fda approved arthrotec. The serum protein binding of misoprostol acid isless than 90% and is concentration-independent in the therapeutic range fda approved arthrotec. After oral administration of radiolabeled misoprostol, about 70% of detectedradioactivity appears in the urine fda approved arthrotec. Maximum plasma concentrations of misoprostolacid are diminished when the dose is taken with food, and total availabilityof misoprostol acid is reduced by use of concomitant antacid fda approved arthrotec. Clinical trialswere conducted with concomitant antacid; this effect does not appear to be clinicallyimportant fda approved arthrotec. Pharmacokinetic studies also showed a lack of drug interaction with antipyrineor propranolol given with misoprostol fda approved arthrotec. Misoprostol given for 1 week had no effecton the steady state pharmacokinetics of diazepam when the two drugs were administered2 hours apart fda approved arthrotec. Pharmacokinetics of ARTHROTEC Table 1 fda approved arthrotec. MISOPROSTOL ACID Mean (SD) The rate and extent of absorption of both diclofenac sodium and misoprostolacid from ARTHROTEC 50 and 75 are similar to those from diclofenac sodium andmisoprostol formulations each administered alone fda approved arthrotec. Neither diclofenac sodium nor misoprostol acid accumulated in plasma followingrepeated doses of ARTHROTEC given every 12 hours under fasted conditions fda approved arthrotec. Fooddecreases the multiple-dose bioavailability profile of ARTHROTEC 50 and ARTHROTEC75 fda approved arthrotec. Special populations A 4-week study, comparing plasma level profiles of diclofenac (50 mg bid) inyounger (26-46 years) versus older (66-81 years) adults, did not show differencesbetween age groups (10 patients per age group) fda approved arthrotec. In a multiple-dose (bid) cross-overstudy of 24 people aged 65 years or older, the misoprostol contained in ARTHROTECdid not affect the pharmacokinetics of diclofenac sodium fda approved arthrotec. Differences in the pharmacokinetics of diclofenac have not been detected instudies of patients with renal (50 mg intravenously) or hepatic impairment (100mg oral solution) fda approved arthrotec. In patients with renal impairment (N=5, creatinine clearance3 to 42 mL/min), AUC values and elimination rates were comparable to those inhealthy people fda approved arthrotec. In patients with biopsy-confirmed cirrhosis or chronic activehepatitis (variably elevated transaminases and mildly elevated bilirubins, N=10),diclofenac concentrations and urinary elimination values were comparable tothose in healthy people fda approved arthrotec. Pharmacokinetic studies with misoprostol in patients with varying degrees ofrenal impairment showed an approximate doubling of t 1/2 , C max and AUC comparedto healthy people fda approved arthrotec. In people over 64 years of age, the AUC for misoprostol acidis increased fda approved arthrotec. Misoprostol does not affect the hepatic mixed function oxidase (cytochromeP-450) enzyme system in animals fda approved arthrotec. In a study of people with mild to moderatehepatic impairment, mean misoprostol acid AUC and C max showed approximatelydouble the mean values obtained in healthy people fda approved arthrotec. Three people who had thelowest antipyrine and lowest indocyanine green clearance values had the highestmisoprostol acid AUC and C max values fda approved arthrotec. |
|||
 
|
|||
|
|
|||
|
|
|||
|
|
|||
|
|
|||
|
|
|||
| ffda approved arthrotec fdda approved arthrotec fdaa approved arthrotec fda approved arthrotec fda aapproved arthrotec fda appproved arthrotec fda appproved arthrotec fda apprroved arthrotec fda approoved arthrotec fda approvved arthrotec fda approveed arthrotec fda approvedd arthrotec fda approved arthrotec fda approved aarthrotec fda approved arrthrotec fda approved artthrotec fda approved arthhrotec fda approved arthrrotec fda approved arthrootec fda approved arthrottec fda approved arthroteec fda approved arthrotecc da approved arthrotec fa approved arthrotec fd approved arthrotec fdaapproved arthrotec fda pproved arthrotec fda aproved arthrotec fda aproved arthrotec fda appoved arthrotec fda apprved arthrotec fda approed arthrotec fda approvd arthrotec fda approve arthrotec fda approvedarthrotec fda approved rthrotec fda approved athrotec fda approved arhrotec fda approved artrotec fda approved arthotec fda approved arthrtec fda approved arthroec fda approved arthrotc fda approved arthrote f da approved arthrotec fd a approved arthrotec fda approved arthrotec fda approved arthrotec fda a pproved arthrotec fda ap proved arthrotec fda app roved arthrotec fda appr oved arthrotec fda appro ved arthrotec fda approv ed arthrotec fda approve d arthrotec fda approved arthrotec fda approved arthrotec fda approved a rthrotec fda approved ar throtec fda approved art hrotec fda approved arth rotec fda approved arthr otec fda approved arthro tec fda approved arthrot ec fda approved arthrote c fda approved arthrotec dfa approved arthrotec fad approved arthrotec fd aapproved arthrotec fdaa pproved arthrotec fda paproved arthrotec fda approved arthrotec fda aprpoved arthrotec fda apporved arthrotec fda apprvoed arthrotec fda approevd arthrotec fda approvde arthrotec fda approve darthrotec fda approveda rthrotec fda approved rathrotec fda approved atrhrotec fda approved arhtrotec fda approved artrhotec fda approved arthortec fda approved arthrtoec fda approved arthroetc fda approved arthrotce afda approved arthrotec thefda approved arthrotec fda approved arthrotec | |||
|
|
|||
|
|
|||
|
|
|||
|
Copyright 2005 D-S LTD. |
