SUCRALFATE TABLETS, USP DESCRIPTION Sucralfate is an ␣-D-glucopy- ranoside, ␤-D-fructofuranosyl-, octakis-(hydrogen sulfate), alu- minum complex.
Tablets for oral administrationcontain 1 g of sucralfate, USP.
nesium stearate, and colloidalsilicon dioxide. CLINICAL PHARMACOLOGY Sucralfate is only minimally absorbed from the gastrointestinal tract. The small amounts of the sulfated disaccharide that are absorbed are excreted primarily in the urine.
sucralfate’s ability to acceleratehealing of duodenal ulcers remainsto be fully defined, it is known that itexerts its effect through a local,rather than systemic, action. Thefollowing observations also appearpertinent:1. Studies in human subjects and
with animal models of ulcerdisease have shown that sucral-fate forms an ulcer-adherentcomplex with proteinaceousexudate of the ulcer site.
film provides a barrier to dif-fusion of hydrogen ions.
given in doses recommended forulcer therapy inhibits pepsinactivity in gastric juice by 32%.
4. In vitro, sucralfate absorbs bile
sucralfate’s antiulcer activity is theresult of formation of an ulcer-adherent complex that covers theulcer site and protects it againstfurther attack by acid, pepsin, andbile salts. There are approximately14 to 16 mEq of acid-neutralizingcapacity per 1-g dose of sucralfate. Clinical Trials Acute Duodenal Ulcer Over 600 patients have participated in well-controlled clinical trials worldwide. Multicenter trials con- ducted in the United States, both of them placebo-controlled studies with endoscopic evaluation at 2 and 4 weeks showed: Treatment Groups Ulcer Healing/No. Patients Treatment Groups Ulcer Healing/No. Patients
The sucralfate-placebo differenceswere statistically significant in bothstudies at 4 weeks but not at 2weeks. The poorer result in the firststudy may have occurred becausesucralfate was given 2 hours aftermeals and at bedtime rather than 1 hour before meals and at bedtime,
the regimen used in internationalstudies and in the second UnitedStates study. In addition, in the firststudy liquid antacid was utilized asneeded, whereas in the secondstudy antacid tablets were used. Maintenance Therapy After Healing of Duodenal Ulcer Two double-blind randomized placebo-controlled U.S. multicenter trials have demonstrated that sucralfate (1 g bid) is effective as maintenance therapy following healing of duodenal ulcers.
performed monthly for 4 months. Ofthe 254 patients who enrolled, 239were analyzed in the intention-to-treat life table analysis presentedbelow. Duodenal Ulcer Recurrence Rate (%)
In this study, prn antacids were notpermitted.
endoscopies were performed at 6 and 12 months, but for-causeendoscopies, were permitted assymptoms dictated. Median symp-tom scores between the sucralfateand placebo groups were notsignificantly different. A life tableintention-to-treat analysis for the 94patients enrolled in the trial had thefollowing results:
Duodenal Ulcer Recurrence Rate (%)
In this study, prn antacids werepermitted.
studies longer than 1 year are notavailable. INDICATIONS AND USAGE Sucralfate tablets, USP are indicated in: • Short-term treatment (up to 8
weeks) of active duodenal ulcer. While healing with sucralfate mayoccur during the first week or two,treatment should be continued for4 to 8 weeks unless healing hasbeen demonstrated by x-ray orendoscopic examination.
ulcer patients at reduced dosageafter healing of acute ulcers. CONTRAINDICATIONS There are no known contraindi- cations to the use of sucralfate. PRECAUTIONS Duodenal ulcer is a chronic, recur- rent disease. While short-term treatment with sucralfate can result in complete healing of the ulcer, a successful course of treatment with sucralfate should not be expected to alter the posthealing frequency or severity of duodenal ulceration. Special Populations: Chronic Renal Failure and Dialysis Patients When sucralfate is administered orally, small amounts of aluminum are absorbed from the gastrointestinal tract. Concomitant use of sucralfate with other products that contain aluminum, such as a l u m i n u m - c o n t a i n i n g antacids, may increase the total body burden of aluminum. Patients with normal renal function receiving the recom- mended doses of sucralfate and aluminum- containing products adequately excrete aluminum in the urine. Patients with chronic renal failure or those receiving dialysis have impaired excretion of absorbed aluminum. In addition, aluminum does not cross dialysis membranes because it is bound to albumin and transferrin plasma proteins. Aluminum accumulation and toxicity (aluminum osteodystrophy, osteo- malacia, encephalopathy) have been described in patients with renal impairment. Sucralfate should be used with caution in patients with chronic renal failure. Drug Interactions Some studies have shown that simultaneous sucralfate adminis- tration in healthy volunteers reduced the extent of absorption (bioavail- ability) of single doses of the following: cimetidine, digoxin, fluoroquinolone, antibiotics, keto- conazole, l-thyroxine, phenytoin, quinidine, ranitidine, tetracycline, and theophylline. Subtherapeutic prothrombin times with con- comitant warfarin and sucralfate therapy have been reported in spontaneous and published case reports. However, two clinical studies have demonstrated no change in either serum warfarin concentration or prothrombin time with the addition of sucralfate to chronic warfarin therapy.
interactions appears to be non-systemic in nature, presumablyresulting from sucralfate binding tothe concomitant agent in thegastrointestinal tract. In all casesstudied to date (cimetidine,ciprofloxacin, digoxin, norfloxacin,ofloxacin, and ranitidine) dosingthe concomitant medication 2 hoursbefore sucralfate eliminated theinteraction. Because of the potentialof sucralfate to alter the absorptionof some drugs, sucralfate should beadministered separately from otherdrugs when alterations in bioavail-ability are felt to be critical. In thesecases, patients should be monitoredappropriately. SUCRALFATE TABLETS, USP Carcinogenesis, Mutagenesis, Impairment of Fertility Chronic oral toxicity studies of 24 months’ duration were conducted in mice and rats at doses up to 1 g/kg (12 times the human dose). There was no evidence of drug- related tumorigenicity. A repro- duction study in rats at doses up to 38 times the human dose did not reveal any indication of fertility impairment. Mutagenicity studies were not conducted. Pregnancy Teratogenic effects. Pregnancy Category B. Teratogenicity studies have been performed in mice, rats and rabbits at doses up to 50 times the human dose and have revealed no evidence of harm to the fetus due to sucralfate. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when sucralfate is administered to a nursing woman. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use Clinical studies of Sucralfate Tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. (See DOSAGE AND ADMINISTRATION)
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. (See PRECAUTIONS Special Populations: Chronic Renal Failure and Dialysis Patients) Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. ADVERSE REACTIONS Adverse reactions to sucralfate in clinical trials were minor and only rarely led to discontinuation of the drug. In studies involving over 2700 patients treated with sucralfate tablets, adverse effects were reported in 129 (4.7%).
frequent complaint (2%). Otheradverse effects reported in lessthan 0.5% of the patients are listedbelow by body system:
Gastrointestinal: diarrhea, nausea, vomiting, gastric discomfort, indigestion, flatulence, dry mouth. Dermatological: pruritus, rash Nervous System: dizziness, insomnia, sleepiness, vertigo Other: back pain, headache
sensitivity reactions, includingurticaria (hives), angioedema,respiratory difficulty, rhinitis,laryngospasm, and facial swellinghave been reported in patientsreceiving sucralfate tablets. Similarevents were reported withsucralfate suspension. However, acausal relationship has not beenestablished.
patients treated with sucralfate. The majority of patients hadunderlying medical conditions thatmay predispose to bezoar for-mation (such as delayed gastricemptying) or were receivingconcomitant enteral tube feedings.
insoluble sucralfate and itsinsoluble excipients has led to fatalcomplications, including pul-monary and cerebral emboli. Sucralfate is not intended forintravenous administration. OVERDOSAGE Due to limited experience in humans with overdosage of sucralfate, no specific treatment recommendations can be given. Acute oral toxicity studies in animals, however, using doses up to 12 g/kg body weight, could not find a lethal dose. Sucralfate is only minimally absorbed from the gastrointestinal tract. Risks associated with acute overdosage should, therefore, be minimal. In rare reports describing sucralfate overdose, most patients remained asymptomatic. Those few reports where adverse events were described included symptoms of dyspepsia, abdominal pain, nausea, and vomiting. DOSAGE AND ADMINISTRATION Active Duodenal Ulcer: The recommended adult oral dosage for duodenal ulcer is 1 g four times a day on an empty stomach.
needed for relief of pain but shouldnot be taken within one-half hourbefore or after sucralfate.
may occur during the first week ortwo, treatment should be continuedfor 4 to 8 weeks unless healing hasbeen demonstrated by x-ray orendoscopic examination. Maintenance Therapy: The recom- mended adult oral dosage is 1 g twice a day. Elderly: In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. (See PRECAUTIONS Geriatric Use) HOW SUPPLIED Sucralfate 1-g tablets, USP are supplied in bottles of 100 and 500. White, scored, oblong tablets embossed with “N” and “S1”.
Bottles of 100 . . . . . NDC 29033-003-01Bottles of 500 . . . . . NDC 29033-003-05
Store at 20°-25°C (68°-77°F) (SeeUSP Controlled Room Temperature).
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X-ray absorption spectroscopy of single-crystalline „ VO … 2P2O7: Electronic structure and possible exchange paths S. Gerhold, N. Nu¨cker, C. A. Kuntscher,* and S. Schuppler Forschungszentrum Karlsruhe, IFP, P.O. Box 3640, D-76021 Karlsruhe, Germany Naval Research Laboratory, Code 6345, Washington DC 20375 A. V. Prokofiev,† F. Bu¨llesfeld, and W. Assmus Kristall- und Material