ULSANIC

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Sucralfate1g

Croscarmellosesodium,polyethyleneglycol,magnesiumstearate,microcrystallinecellulose.

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065812289711

ChugaiPharmaceuticalCompanyLtd,Tokyo,Japan

" עעבקנהזןולעטמרופ " רשואוקדבנונכותותואירבהדרשמי ." רשואמןולע : רבמבונ 2011 .

“This leaflet format has been determined by the Ministryof Healthand thecontent thereof has been

checked and approved.” Dateof approval:November 2011.

ULSANIC ®

TABLETS

Composition

Each tablet contains:

Active Ingredient

Sucralfate 1 g

Other Ingredients

Croscarmellose sodium, polyethylene glycol, magnesium stearate,microcrystalline

cellulose.

Sodiumcontent: 2.5-3.7 mgper tablet.

Action

Ulsanic is a non-systemic anti-ulcer drug which actslocallyinthegastrointestinal

tract at the ulcer site.

Sucralfate is not an antacid; it has negligibleacid-neutralizingcapacityanditsanti-

ulcer effects cannot be attributed to neutralization of gastric acid.

Sucralfate forms a protective barrier at the ulcer site. It reacts withproteinaceous

exudates such as albumin and fibrinogen present in the ulcer crater, toformastable

chemicalcomplex.This complex binds selectively to the damaged mucosa, creating a

barrier, which prevents further tissue damage. The coating, which forms at the crater,

blocks the passage of erosive substances such as gastric acid and pepsin to the ulcer

site, thus protecting the tissues and promoting healing.

Sucralfate has beenfoundin vitroto inhibit the aggressive action of pepsin to

absorb bile salts.

Sucralfate is virtually unabsorbed from thegastrointestinaltractandthisresultsin

no significant systemic adverse effects.

Indications

Ulsanic is indicated in the short-term treatment of duodenal ulcer and gastric ulcer.

Contraindications

Known hypersensitivity to any ingredient of the preparation.

Patients with severe renal dysfunction or patients receiving dialysis,sincelong-term

administration of this product may causealuminiumencephalopathyaluminium

osteomalacia and anemia.

Warnings

The product should only be used with caution in patients with renal dysfunction,due

to the possibility of increased aluminium absorption.Theconcomitantuseofother

aluminium containing medications is not recommendedinviewoftheenhanced

potential for aluminium absorption and toxicity.

Bezoars(aninsolublemass formed within the gastric lumen) have been reported

occasionally in patients taking this product. The majority of these patients had

underlyingconditionsthatmaypredispose to bezoar formation such as delayed

gastric emptying, or were receiving concomitantenteralfeeding(seeunder

Interactions).

Bezoarshavebeenreportedafteradministration of Ulsanic to severely ill patients,

especially in premature infants in whomthe use of sucralfate is not recommended.

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Mutagenicity

Mutagenicity studies were not conducted.

Carcinogenicity

Chronicoraltoxicitystudies of 24 months' duration were conducted in mice and rats

at doses up to 1 g/kg (12 times the human dose). There was noevidenceofdrug-

related tumorigenicity.

Effect on Fertility and Reproduction

A reproduction study in rats at doses up to 38timesthehumandosedidnotreveal

any indication of fertility impairment. The effect ofsucralfateonhumanfertilityisnot

known.

Use in Pregnancy

Teratogenicity studies have been performed in mice, ratsandrabbitsatdosesupto

50times the human dose and have revealed no evidence of harm to the fetus due to

sucralfate.Therearehowever, no adequate and well controlled studies in pregnant

women.Becauseanimalreproduction studies are not always predictive of human

response, this drug should be used during pregnancy only if clearly needed.

Use During Lactation

It is not known whether thisdrugisexcreted in human milk. Problems in humans

have not been documented; however, risk-benefit should be considered.

Use in Pediatrics

Safety and effectiveness in children have not been established.

Use in the Elderly

Sincetheelderly often have reduced physiological function, the dosage should be

adjusted with care.

Use in Renal Impairment and Chronic Renal Failure

Patientswithnormalrenal function receiving the recommended doses of sucralfate

andaluminium-containing products adequately excrete aluminium in the urine.

Patientswithchronic renal failure or those receiving dialysis have impaired excretion

ofabsorbed aluminium. In addition, aluminium does not cross dialysis membranes

becauseitis bound to albumin and transferrin plasma proteins. Aluminium

accumulation and toxicity (aluminum osteodystrophy, aluminiumosteomalacia,

anemia, and aluminium encephalopathy) have been described in patientswithrenal

impairment. Sucralfate should be used with caution in patientswithchronicrenal

failure,and the blood concentrations of aluminium, phosphate, calcium, alkaline

phosphatase should be periodically measured.

Use in Dialysis Patients

See Contraindications.

Adverse Reactions

Adversereactionstosucralfatein clinical trials were minor, of low incidence, and

only rarely led to discontinuation of the drug.

Constipation was the most frequent complaint (2%). Other adverse effects, reported

in less than 0.5% of the patients, are listed below by body system:

Gastrointestinal: Diarrhea, nausea, vomiting, gastricdiscomfort,indigestion,

flatulence, dry mouth.

Thirst has also been reported.

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Dermatological: Pruritus, rash, urticaria, edema.

Central Nervous System: Dizziness, drowsiness, headache, sleepiness, vertigo.

Other:Back pain.

Postmarketingreports of hypersensitivity reactions, including anaphylactic reactions,

urticaria (hives), angioedema, respiratory difficulty, and rhinitis havebeenreceived.

However, a causal relationship has not been established.

Precautions

Duodenal ulcer is a chronic recurrent disease.Whileshort-termtreatmentwith

Ulsaniccanresultincompletehealingof the ulcer, a successful course of treatment

withUlsanicshouldnot be expected to alter the post-healing frequency or severity of

duodenal ulceration.

Cautionshouldbeexercised when administering sucralfate to patients with

phosphatedeficiencies, since the aluminium in the sucralfate molecule binds to

phosphate in the gastrointestinal tract and inhibits its absorption.

Long-TermAdministration:

Caution should be exercised because long-term administration ofthisproductmay

cause symptoms such as aluminium encephalopathy, aluminiumosteomalacia,

anemia, and aluminium osteodystrophy.

Effects on abilityto drive and use machines

Do not drive if you feel dizzy or drowsy.

Drug Interactions

The amount of free aluminium ions liberated from sucralfate in the gastrointestinal

tract is insignificant. Nevertheless, it is prudent to recommend a lapseof2hours

between the ingestion of sucralfate and other oral medications, to preventpossible

reducedtherapeuticefficacydue to aluminium ion chelation. Special caution is

required when the patient is being treated with oral tetracyclines.

The same precaution also applies if milk or dairy products are to be ingested.

Concurrent use of sucralfate and aluminium-containingmedicationsinpatientswith

renal failure may cause aluminium toxicity.

Simultaneous administration of sucralfate and antacidsinnotrecommended,since

antacidsmayinterferewith binding of sucralfate to the mucosa. It is therefore

recommended not to take antacids within 1 hour before or after sucralfate.

Some studies have shown that simultaneous sucralfate administration in healthy

volunteers reduced the extent of absorption (bioavailability) of the following drugs:

cimetidine,ofloxacin, ciprofloxacin, digoxin, norfloxacin, phenytoin, ranitidine,

tetracycline, sulpiride, ketoconazole, warfarin, thyroxine,quinidine,H2-antagonists

andtheophylline.Themechanismof these interactions appears to be nonsystemic in

nature, presumably resulting from sucralfate binding to the concomitantagentinthe

gastrointestinal tract. The bioavailability of these agents may be restored by

separating the administration of these agents from Ulsanic by two hours. In allcases

studied to date (cimetidine, ciprofloxacin, digoxin, and ranitidine), dosing the

concomitant medication 2hours before sucralfateeliminatedtheinteraction.Because

of the potential of sucralfate to alter the absorption of some other drugs,sucralfate

should be administered separately from otherdrugswhenalterationsinbioavailability

are felt to be critical. In these cases, patients should be monitored appropriately.

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The administration of Ulsanic Tablets and enteral feeds by nasogastrictubeshould

be separated by one hour in patients receivingUlsanicTabletsfortheprophylaxisof

stress ulceration. In rare cases bezoar formation has beenreportedwhenUlsanicand

enteral feeds have been given too closely together. Therefore patients shouldbe

carefully observed, and, if the development of bezoarissuspected,thedrugshould

be discontinued and appropriate measures must be taken.

Other Drug Interactions

Sucralfate/Citrate Preparations (e.g.potassiumcitrate, sodium citrate):

Coadministrationofthesedrugswith sucralfate may increase the blood

concentrationsofaluminium.Themechanism may be due to chelation of aluminium,

which is assumed to increase its absorption. Therefore combinations of sucralfateand

citrate preparations should not be coadmininstered.

Sucralfate/Ion-Exchange Resins (whichabsorb and thus decrease serum potassium,

calcium, and also aluminium levels suchas calcium polystyrene sulfonate, sodium

polystyrene sulfonate): Concomitant administration may lead toreductioninthe

capacity of the ion-exchange resins.

Sucralfate/Thyroid Hormone Preparations (e.g. Levothyroxine sodium)/Bile Acid

Preparations (e.g. Ursodeoxycholic acid, deoxycholic acid/:Sucralfate may inhibit or

delaythe absorption of these drugs upon concomitant administration (sucralfate

absorbsthese drugs in the gastrointestinal tract). Therefore it is recommended to

increase dosing intervals.

Dosage and Administration

The tablets should not be chewed or crushed. They can be divided.

The recommended adult oral dosage is 1 tablet 4 times a day on an empty stomach,

30 minutes before each meal and at bedtime.

Antacids may be prescribed as needed for relief ofpainbutshouldnotbetaken

within the time-span of 1 hour before or 1 hour after Ulsanic.

While healing with Ulsanic may occur during thefirstweekortwo,treatmentshould

be continued for 4-8 weeks unless X-rayorendoscopicexaminationhas

demonstrated healing.

Overdosage

There is no experience in humans with overdosage. Oral toxicitystudiesconducted

inanimals,however, using doses up to 12g/kg bodyweight, could not establish a

lethal dose. Therefore, risks associated with overdosage are believed to be minimal.

STORAGE

Store in a dry place, below 25 C.

Registration Number:

065.81.22897.11.

Teva Pharmaceutical Industries Ltd

P.O.Box 3190, Petach Tikva.

Under license from

Chugai Pharmaceutical Company Ltd., Tokyo, Japan

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