SUCRALFATE
DESCRIPTION:
SUCRAMAL (sucralfate) is an alpha-D- glucopyranoside, beta-D-fructofuranosyl-,
octakis-(hydrogen sulfate), aluminum complex.
R=SO3Al2(OH)2)
SUCRAMAL Suspension for oral administration contains 1 g of sucralfate per 10
mL.
SUCRAMAL Suspension also contains: colloidal silicon dioxide NF, FD&C Red #40,
flavor, glycerin USP, methylcellulose USP, methylparaben NF, microcrystalline
cellulose NF, purified water USP, simethicone USP, and sorbitol solution USP.
Therapeutic category: antiulcer.
ACTIONS/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.
Although the mechanism of sucralfate's ability to accelerate healing of duodenal
ulcers remains to be fully defined, it is known that it exerts its effect
through a local, rather than systemic, action. The following observations also
appear pertinent:
1. Studies in human subjects and with animal models of ulcer disease have shown
that sucralfate forms an ulcer-adherent complex with proteinaceous exudate at
the ulcer site.
2. In vitro, a sucralfate-albumin film provides a barrier to diffusion of
hydrogen ions.
3. In human subjects, sucralfate given in doses recommended for ulcer therapy
inhibits pepsin activity in gastric juice by 32%.
4. In vitro, sucralfate adsorbs bile salts.
These observations suggest that sucralfate's antiulcer activity is the result of
formation of an ulcer-adherent complex that covers the ulcer site and protects
it against further attack by acid, pepsin, and bile salts. There are
approximately 14-16 mEq of acid-neutralizing capacity per 1-g dose of
sucralfate.
CLINICAL STUDIES:
CLINICAL TRIALS
In a multicenter, double-blind, placebo- controlled study of SUCRAMAL
Suspension, a dosage regimen of 1 g (10 mL) four times daily was demonstrated to
be superior to placebo in ulcer healing.
RESULTS FROM CLINICAL TRIALS
HEALING RATES FOR ACUTE DUODENAL ULCER
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Week 2 Week 4 Week 8
Healing Healing Healing
Treatment n Rates Rates Rates
-----------------------------------------------------------------------------------------------------------------------------------
SUCRAMAL 145 23(16%)* 66(46%)** 95(66%)*/*
Suspension
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Placebo 147 10(7%) 39(27%) 58(39%)
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* P=0.016 **P=0.001 */*P= 0.0001
Equivalence of sucralfate suspension to sucralfate tablets has not been
demonstrated.
INDICATIONS AND USAGE:
SUCRAMAL (sucralfate) Suspension is indicated in the short-term (up to 8 weeks)
treatment of active duodenal ulcer.
CONTRAINDICATIONS:
There are no known contraindications to the use of sucralfate.
PRECAUTIONS:
Duodenal ulcer is a chronic, recurrent 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 aluminum-containing antacids, may
increase the total body burden of aluminum. Patients with normal renal function
receiving the recommended 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, osteomalacia, 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 administration in healthy
volunteers reduced the extent of absorption (bioavailability) of single doses of
the following: cimetidine, digoxin, fluoroquinolone antibiotics, ketoconazole,
l-thyroxine, phenytoin, quinidine, ranitidine, tetracycline, and theophylline.
Subtherapeutic prothrombin times with concomitant 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.
The mechanism of these interactions appears to be nonsystemic in nature,
presumably resulting from sucralfate binding to the concomitant agent in the
gastrointestinal tract. In all cases studied to date (cimetidine, ciprofloxacin,
digoxin, norfloxacin, ofloxacin, and ranitidine), dosing the concomitant
medication 2 hours before sucralfate eliminated the interaction. Because of the
potential of SUCRAMAL to alter the absorption of some drugs, SUCRAMAL should be
administered separately from other drugs when alterations in bioavailability are
felt to be critical. In these cases, patients should be monitored appropriately.
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 reproduction 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 sulcralfate. 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.
DRUG INTERACTIONS:
Some studies have shown that simultaneous sucralfate administration in healthy
volunteers reduced the extent of absorption (bioavailability) of single doses of
the following: cimetidine, digoxin, fluoroquinolone antibiotics, ketoconazole,
l-thyroxine, phenytoin, quinidine, ranitidine, tetracycline, and theophylline.
Subtherapeutic prothrombin times with concomitant 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.
The mechanism of these interactions appears to be nonsystemic in nature,
presumably resulting from sucralfate binding to the concomitant agent in the
gastrointestinal tract. In all cases studied to date (cimetidine, ciprofloxacin,
digoxin, norfloxacin, ofloxacin, and ranitidine), dosing the concomitant
medication 2 hours before sucralfate eliminated the interaction. Because of the
potential of SUCRAMAL to alter the absorption of some drugs, SUCRAMAL should be
administered separately from other drugs when alterations in bioavailability are
felt to be critical. In these cases, patients should be monitored appropriately.
(See Also PRECAUTIONS)
ADVERSE REACTIONS:
Adverse reactions to sucralfate tablets in clinical trials were minor and only
rarely led to discontinuation of the drug. In studies involving over 2700
patients treated with sucralfate, adverse effects were reported in 129 (4.7%).
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, dry mouth, flatulence, gastric discomfort,
indigestion, nausea, vomiting
DERMATOLOGICAL: pruritus, rash
NERVOUS SYSTEM: dizziness, insomnia, sleepiness, vertigo
OTHER: back pain, headache
Postmarketing reports of hypersensitivity reactions, including urticaria
(hives), angioedema, respiratory difficulty, rhinitis, laryngospasm, and facial
swelling have been reported in patients receiving sucralfate tablets. Similar
events were reported with sucralfate suspension. However, a causal relationship
has not been established.
Bezoars have been reported in patients treated with sucralfate. The majority of
patients had underlying medical conditions that may predispose to bezoar
formation (such as delayed gastric emptying) or were receiving concomitant
enteral tube feedings.
Inadvertent injection of insoluble sucralfate and its insoluble excipients has
led to fatal complications, including pulmonary and cerebral emboli. Sucralfate
is not intended for intravenous administration.
OVERDOSAGE:
Due to limited experience in humans with overdosage of sucralfate, no specific
treatment recommendations can be given. Acute oral 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 (10 mL/2 teaspoonfuls) four times per day. SUCRAMAL should be administered
on an empty stomach.
Antacids may be prescribed as needed for relief of pain but should not be taken
within one-half hour before or after sucralfate.
While healing with sucralfate may occur during the first week or two, treatment
should be continued for 4 to 8 weeks unless healing has been demonstrated by x-
ray or endoscopic examination.
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