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how long has arthrotec 50 been on the market Manufacturer: Searle (diclofenac sodium and misoprostol) tablets
PATIENTS MUST BE ADVISED OF THE ABORTIFACIENT PROPERTY AND WARNED NOT TO GIVETHE DRUG TO OTHERS how long has arthrotec 50 been on the market. UTERINE RUPTURE HAS BEEN REPORTED WHEN MISOPROSTOL WAS ADMINISTERED INTRAVAGINALLYIN PREGNANT WOMEN TO INDUCE LABOR OR TO INDUCE ABORTION BEYOND THE FIRST TRIMESTEROF PREGNANCY how long has arthrotec 50 been on the market. UTERINE PERFORATION HAS BEEN REPORTED FOLLOWING ADMINISTRATION OF COMBINEDVAGINAL-AND-ORAL MISOPROSTOL IN PREGNANT WOMEN TO INDUCE ABORTION how long has arthrotec 50 been on the market. IN EACH OFTHESE REPORTED CASES, THE GESTATIONAL AGE OF THE PREGNANCIES WAS UNKNOWN how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. (See WARNINGS ) how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. Diclofenac sodium is freely solublein methanol, soluble in ethanol and practically insoluble in chloroform andin dilute acid how long has arthrotec 50 been on the market. Diclofenac sodium is sparingly soluble in water how long has arthrotec 50 been on the market. Its chemicalformula and name are: C 14 H 10 Cl 2 NO 2 Na [M.W how long has arthrotec 50 been on the market. = 318.14] 2-[ (2, 6-dichlorophenyl) amino] benzeneaceticacid, monosodium salt how long has arthrotec 50 been on the market. Misoprostol is a water-soluble, viscous liquid that contains approximatelyequal amounts of two diastereomers how long has arthrotec 50 been on the market. Its chemical formula and name are: C 22 H 38 O 5 [M.W how long has arthrotec 50 been on the market. = 382.54] (±)methyl 11(alpha), 16-dihydroxy-16-methyl-9-oxoprost-13E-en-1-oate how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market.
Diclofenac sodium is completely absorbed from the GI tract after fasting, oraladministration how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. Only 50% of the absorbeddose is systemically available due to first pass metabolism how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. Peak plasmalevels are less than dose proportional and are approximately 1.5 and 2.0 mcg/mLfor 50 mg and 75 mg doses, respectively how long has arthrotec 50 been on the market. Plasma concentrations of diclofenac sodium decline from peak levels in a biexponentialfashion, with the terminal phase having a half-life of approximately 2 hours how long has arthrotec 50 been on the market. Clearance and volume of distribution are about 350 mL/min and 550 mL/kg, respectively how long has arthrotec 50 been on the market. More than 99% of diclofenac sodium is reversibly bound to human plasma albumin how long has arthrotec 50 been on the market. Diclofenac sodium is eliminated through metabolism and subsequent urinary andbiliary excretion of the glucuronide and the sulfate conjugates of the metabolites how long has arthrotec 50 been on the market. Approximately 65% of the dose is excreted in the urine and 35% in the bile how long has arthrotec 50 been on the market. Conjugates of unchanged diclofenac account for 5-10% of the dose excreted inthe urine and for less than 5% excreted in the bile how long has arthrotec 50 been on the market. Little or no unchangedunconjugated drug is excreted how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. Conjugates of three other metabolites together account for 10-20% of the doseexcreted in the urine and for small amounts excreted in the bile how long has arthrotec 50 been on the market. The eliminationhalf-life values for these metabolites are shorter than those for the parentdrug how long has arthrotec 50 been on the market. Urinary excretion of an additional metabolite (half-life = 80 hours) accountsfor only 1.4% of the oral dose how long has arthrotec 50 been on the market. The degree of accumulation of diclofenac metabolitesis unknown how long has arthrotec 50 been on the market. Some of the metabolites may have activity how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. In vitro studies on canine parietal cells using tritiated misoprostol acidas the ligand have led to the identification and characterization of specificprostaglandin receptors how long has arthrotec 50 been on the market. Receptor binding is saturable, reversible, and stereospecific how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. Receptor-site affinityfor misoprostol correlates well with an indirect index of antisecretory activity how long has arthrotec 50 been on the market. It is likely that these specific receptors allow misoprostol taken with foodto be effective topically, despite the lower serum concentrations attained how long has arthrotec 50 been on the market. Misoprostol produces a moderate decrease in pepsin concentration during basalconditions, but not during histamine stimulation how long has arthrotec 50 been on the market. It has no significant effecton fasting or postprandial gastrin nor intrinsic factor output how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. Activity is apparent 30 minutes after oral administration and persists for atleast 3 hours how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. Orally administered misoprostol is rapidly and extensively absorbed, and itundergoes rapid metabolism to its biologically active metabolite, misoprostolacid how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. No accumulationof misoprostol acid was found in multiple-dose studies, and plasma steady statewas achieved within 2 days how long has arthrotec 50 been on the market. The serum protein binding of misoprostol acid isless than 90% and is concentration-independent in the therapeutic range how long has arthrotec 50 been on the market. After oral administration of radiolabeled misoprostol, about 70% of detectedradioactivity appears in the urine how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. Clinical trialswere conducted with concomitant antacid; this effect does not appear to be clinicallyimportant how long has arthrotec 50 been on the market. Pharmacokinetic studies also showed a lack of drug interaction with antipyrineor propranolol given with misoprostol how long has arthrotec 50 been on the market. Misoprostol given for 1 week had no effecton the steady state pharmacokinetics of diazepam when the two drugs were administered2 hours apart how long has arthrotec 50 been on the market. Pharmacokinetics of ARTHROTEC Table 1 how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. Neither diclofenac sodium nor misoprostol acid accumulated in plasma followingrepeated doses of ARTHROTEC given every 12 hours under fasted conditions how long has arthrotec 50 been on the market. Fooddecreases the multiple-dose bioavailability profile of ARTHROTEC 50 and ARTHROTEC75 how long has arthrotec 50 been on the market. 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) how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. Differences in the pharmacokinetics of diclofenac have not been detected instudies of patients with renal (50 mg intravenously) or hepatic impairment (100mg oral solution) how long has arthrotec 50 been on the market. In patients with renal impairment (N=5, creatinine clearance3 to 42 mL/min), AUC values and elimination rates were comparable to those inhealthy people how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. In people over 64 years of age, the AUC for misoprostol acidis increased how long has arthrotec 50 been on the market. Misoprostol does not affect the hepatic mixed function oxidase (cytochromeP-450) enzyme system in animals how long has arthrotec 50 been on the market. 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 how long has arthrotec 50 been on the market. Three people who had thelowest antipyrine and lowest indocyanine green clearance values had the highestmisoprostol acid AUC and C max values how long has arthrotec 50 been on the market. |
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