This information is intended for use by health professionals

1. Name of the medicinal product

Antepsin 1g Tablets

2. Qualitative and quantitative composition

Each tablet contains 1 gram of sucralfate.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Tablet

Biconvex, oblong, white tablets with a dividing score on one side.

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

4. Clinical particulars
4.1 Therapeutic indications

Antepsin is indicated in adults and adolescents over 14 years old for treatment of duodenal ulcer, gastric ulcer, chronic gastritis.

4.2 Posology and method of administration

For oral administration.

Duodenal ulcer, gastric ulcer, chronic gastritis:

Adults: The usual dose is 2 grams twice daily to be taken on rising and at bedtime, or 1 gram 4 times a day to be taken 1 hour before meals and at bedtime. Maximum daily dose: 8 grams. For ease of administration, Antepsin Tablets may be dispersed in 10-15 mL of water. Four to six weeks' treatment is usually needed for ulcer healing, but up to twelve weeks may be necessary in resistant cases.

Antacids may be used as required for relief of pain, but should not be taken half an hour before or after Antepsin.

Elderly: There are no special dosage requirements for elderly patients but, as with all medicines, the lowest effective dose should be used.

Paediatric population: The safety and efficacy of Antepsin in children under 14 years of age has not been established. Currently available data are described in section 5.1 but no recommendation on posology can be made.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

The product should only be used with caution in patients with renal dysfunction, due to the possibility of increased aluminium absorption.

Sucralfate is not recommended for use in individuals on dialysis.

In patients with severe or chronic renal impairment, Antepsin should be used with extreme caution and only for short-term treatment. . Small amounts of aluminium are absorbed through the gastrointestinal tract and aluminium may accumulate. Aluminium osteodystrophy, osteomalacia, encephalopathy, and anaemia have been reported in patients with chronic renal impairment. For patients with impairment of renal function, laboratory testing such as aluminium, phosphate, calcium, and alkaline phosphatase is recommended to be periodically performed due to excretion impairment. The concomitant use of other aluminium containing medications is not recommended in view of the enhanced potential for aluminium absorption and toxicity.

Bezoars have been reported after administration of sucralfate mainly to severely ill patients in intensive care units. The majority of these patients (including neonates in whom sucralfate is not recommended) had underlying conditions that may predispose to bezoar formation (such as delayed gastric emptying due to surgery, drug therapy or diseases that reduce motility), or were receiving concomitant enteral tube feeding.

At the time of taking sucralfate tablets, aspiration may occur in patients with swallowing difficulty.

Paediatric Population

Antepsin is not recommended for use in children under 14 years of age due to insufficient data on safety and efficacy.

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant administration of Antepsin may reduce the bioavailability of certain drugs including fluoroquinolones such as ciprofloxacin and norfloxacin, tetracycline, ketoconazole, sulpiride, digoxin, warfarin, phenytoin, theophylline, levothyroxine, quinidine and H₂ antagonists. The bioavailability of these agents may be restored by separating the administration of these agents from Antepsin by two hours. This interaction appears to be non systemic in origin presumably resulting from these agents being bound by Antepsin in the gastrointestinal tract. Because of the potential of Antepsin to alter the absorption of some drugs from the gastrointestinal tract, the separate administration of Antepsin from that of other agents should be considered when alterations in bioavailability are felt to be critical for concomitantly administered drugs.

Sucralfate should not be co-administered with citrate preparations. Co-administration citrate preparations with sucralfate may increase the blood concentrations of aluminium. The mechanism may be due to chelation of aluminium, which is assumed to increase its absorption.

The administration of Antepsin Tablets 1 g and enteral feeds by nasogastric tube should be separated by one hour in patients receiving Antepsin Tablets 1 g for the prophylaxis of stress ulceration. In rare cases bezoar formation has been reported when Antepsin and enteral feeds have been given too closely together.

4.6 Fertility, pregnancy and lactation

Pregnancy

Teratogenicity studies in mice, rats and rabbits at doses up to 50 times the human dose have revealed no evidence of harm to the foetus. Safety in pregnant women has not been established and Antepsin should be used during pregnancy only if clearly needed.

Lactation

It is not known whether this drug is excreted in human milk. Caution should be exercised when Antepsin is administered to breast-feeding women.

4.7 Effects on ability to drive and use machines

Do not drive if you feel dizzy or drowsy.

4.8 Undesirable effects

Tabulated list of adverse reactions

Immune system disorders

Not known (cannot be estimated from the available data)

Anaphylactic reaction including pruritus, urticaria, oedema, dyspnoea

Nervous system disorders

Not known (cannot be estimated from the available data)

Dizziness, headache, drowsiness

Ear and labyrinth disorders

Not known (cannot be estimated from the available data)

Vertigo

Gastrointestinal disorders

Common (≥ 1% and < 10%);

Constipation

Uncommon (≥ 0.1% and <1%)

Dry mouth, nausea,

Rare (≥ 0.01% and <0.1%)

Bezoar formation¹

Not known (cannot be estimated from the available data)

Diarrhoea, vomiting, gastric discomfort, indigestion, flatulence

Skin and subcutaneous tissue disorders

Rare (≥ 0.01% and <0.1%)

Rash

Musculoskeletal and connective tissue disorders

Not known (cannot be estimated from the available data)

Back pain

Injury, poisoning and procedural complications

Not known (cannot be estimated from the available data)

Osteodystrophy² , osteomalacia² , encephalopathy² , anaemia²

¹Reported in patients with impaired gastric emptying, patients with enteral tube feeding or low birth weight infants

²Reported in patients with chronic renal impairment

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

In a clinical trial on healthy men of overdose with sucralfate, most cases remained asymptomatic, but symptoms of abdominal pain, nausea, and vomiting were reported in a few cases. Acute oral toxicity studies in animals, using doses up to 12g/kg body weight, could not find a lethal dose. Risks associated with overdose, should, therefore, be minimal.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Alimentary tract and metabolism, ATC code: A02B X02

Mechanism of action

The action of Antepsin is non-systemic as the drug is only minimally absorbed from the gastro-intestinal tract. The small amounts that are absorbed are excreted primarily in the urine. Antepsin exerts a generalised cytoprotective effect by preventing gastro-intestinal mucosal injury.

Studies in humans and animal models show that Antepsin forms an ulcer adherent complex with the proteinaceous exudate of the ulcer site. This property enables Antepsin to form a protective barrier over the ulcer lesion giving sustained protection against the penetration and action of gastric acid, pepsin and bile.

Studies both in humans and animals demonstrate that Antepsin protects the gastric mucosa against various irritants such as alcohol, acetylsalicyclic acid and sodium taurocholate.

Antepsin also directly inhibits pepsin activity and absorbs bile salts. It has only weak antacid activity. It does not alter gastric emptying time, nor normal digestive function. Antepsin has no demonstrated pharmacological effect on the cardiovascular or central nervous systems.

Paediatric population

In the literature, there are limited clinical data on the use of sucralfate in children, mainly for stress ulcer prophylaxis, reflux oesophagitis, and mucositis. The dose used in these studies was 0.5 – 1 g four times a day, depending on the children's age and the severity of the underlying disease, and was applied without major safety concerns. In view of the limited data, use of sucralfate in children under 14 years of age is currently not recommended.

5.2 Pharmacokinetic properties

Absorption

Sucralfate is only minimally absorbed from the gastro-intestinal tract. The small amounts that are absorbed are excreted primarily in the urine. Absorption of aluminium from sucralfate may be increased in patients on dialysis or with renal dysfunction (see also “other special warnings and precautions”).

5.3 Preclinical safety data

There was no evidence of carcinogenesis in mice and rats receiving oral sucralfate in dosages of up to 1 g/kg daily (12 times the usual human dosage) for 2 years. In animal studies there was no effect evidence of impaired fertility. The effect of sucralfate on human fertility is not known.

6. Pharmaceutical particulars
6.1 List of excipients

Macrogol 6000

Microcrystalline cellulose

Calcium Carmellose

Magnesium stearate.

6.2 Incompatibilities

Not applicable

6.3 Shelf life

3 years

6.4 Special precautions for storage

Store below 25°C.

6.5 Nature and contents of container

Blister packs (pack size 50 tablets).

6.6 Special precautions for disposal and other handling

No special requirements.

7. Marketing authorisation holder

Chugai Pharma UK Ltd.

Mulliner House

Flanders Road

Turnham Green

London

W4 1NN

U.K.

8. Marketing authorisation number(s)

PL 12185/0008

9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 1 December 1998

Date of latest renewal: 27 April 2001

10. Date of revision of the text

September 2013