PEPCID^® 20 mg Tablets

PEPCID^® 40 mg Tablets

'Pepcid' 20 mg, each tablet contains 20 mg of famotidine.

'Pepcid' 40 mg, each tablet contains 40 mg of famotidine.

Film-coated tablets.

Beige, round-cornered square tablets, marked 'MSD 963' on one side and plain on the other.

Brown, round-cornered square tablets, marked 'MSD 964' on one side and plain on the other.

Duodenal ulcer.

Prevention of relapses of duodenal ulceration.

Benign gastric ulcer.

Hypersecretory conditions such as ZollingerEllison syndrome.

Treatment of gastro-oesophageal reflux disease.

Prevention of relapse of symptoms and erosions or ulcerations associated with gastrooesophageal reflux disease.

In benign gastric and duodenal ulceration, the dose of 'Pepcid' is one 40 mg tablet at night.

Duodenal ulcer

The recommended initial dose is one 40 mg tablet of 'Pepcid' at night. Treatment should continue for four to eight weeks. In most patients, healing occurs on this regimen within four weeks. In those patients whose ulcers have not healed completely after four weeks, a further fourweek period of treatment is recommended.

Maintenance therapy: For preventing the recurrence of duodenal ulceration, the reduced dose of 20 mg of 'Pepcid' at night is recommended.

Benign gastric ulcer

The recommended dose is one 40 mg tablet of 'Pepcid' at night. Treatment should continue for four to eight weeks unless endoscopy reveals earlier healing.

ZollingerEllison syndrome

Patients without prior antisecretory therapy should be started on 20 mg of 'Pepcid' every six hours. Dosage should then be adjusted to individual response: doses up to 800 mg daily have been used up to one year without the development of significant adverse effects or tachyphylaxis. Patients who have been receiving another H₂ antagonist may be switched directly to 'Pepcid' at a dose higher than that recommended for new cases. This starting dose will depend on the severity of the condition and the last dose of H₂ antagonist previously used.

Gastrooesophageal reflux disease

The recommended dosage for the symptomatic relief of gastrooesophageal reflux disease is 20 mg of famotidine twice daily, which may be given for six to twelve weeks. Most patients experience improvement after two weeks.

Where gastro-oesophageal reflux disease is associated with the presence of oesophageal erosion or ulceration, the recommended dosage is 40 mg of famotidine twice daily, which may be given for six to twelve weeks.

Maintenance therapy: For the prevention of recurrence of symptoms and erosions or ulcerations associated with gastrooesophageal reflux disease, the recommended dosage is 20 mg of famotidine twice daily.

Use in the elderly: The recommended dosage in most elderly patients is the same as in younger patients for all indications (see above).

Use in impaired renal function: To avoid excess accumulation of the drug in patients with moderate or severe renal insufficiency, the dose of PEPCID may be reduced to half the dose or the dosing interval may be prolonged to 36-48 hours as indicated by the patient's clinical response.

Paediatric use

The efficacy and safety of 'Pepcid' in children have not been established.

Hypersensitivity to any component of this product. Cross sensitivity in this class of compounds has been observed. Therefore 'Pepcid' should not be administered to patients with a history of hypersensitivity to other H₂-receptor antagonists.

Gastric carcinoma

Gastric malignancy should be excluded prior to initiation of therapy of gastric ulcer with 'Pepcid'. Symptomatic response of gastric ulcer to therapy with 'Pepcid' does not preclude the presence of gastric malignancy.

Impaired renal function

Since 'Pepcid' is primarily excreted via the kidney, caution should be exercised when treating patients with impaired renal function. The dose should be reduced to 20 mg nocte when creatinine clearance falls below 10 ml/min.

'Pepcid' does not inhibit the hepatic cytochrome P450 enzyme system. Furthermore, clinical studies have shown that famotidine does not potentiate the actions of warfarin, theophylline, phenytoin, diazepam, propranolol, aminopyrine and antipyrine, which are inactivated by this system.

Probenecid

The administration of probenecid can delay the elimination of famotidine. Concomitant use of probenecid and famotidine tablets should be used with caution.

Antacids

Bioavailability may be slightly increased by food, or slightly decreased by antacids; however, these effects are of no clinical consequence.

Ketonconazole / Itraconazole

During concomitant use of substances whose absorption is affected by gastric acid levels, a possible change in the absorption of these substances should be considered. The absorption of ketoconazole or itraconazole can be reduced; ketoconazole should be administered two hours before administering famotidine.

Pregnancy: 'Pepcid' is not recommended for use in pregnancy, and should be prescribed only if clearly needed. Before a decision is made to use 'Pepcid' during pregnancy, the physician should weigh the potential benefits from the drug against the possible risks involved.

Breastfeeding mothers: 'Pepcid' is secreted in human milk, therefore breastfeeding mothers should either stop breast-feeding or stop taking the drug.

None known.

General disorders and administration site conditions :

Very rare: fatigue

Nervous system disorders:

Rare: headache, dizziness,

Very rare: epileptic seizures/convulsions (in patients with impaired renal function), paraesthesia

Gastrointestinal disorders:

Rare: constipation, diarrhoea

Very rare: dry mouth, dysgeusia, nausea and/or vomiting, abdominal discomfort of distension, anorexia

Hepatobiliary disorders:

Very rare: liver enzyme abnormalities, cholestatic jaundice

Isolated cases: worsening of hepatic disease however a causal relationship to therapy with 'Pepcid' has not been established.

Skin and subcutaneous tissue disorders:

Very rare: rash, pruritus, Stevens Johnson Syndrome/toxic epidermal necrolysis

Immune system disorders:

Very rare: urticaria, anaphylaxis, angioedema

Musculoskeletal and connective tissue disorders:

Very rare: arthralgia, muscle cramps

Psychiatric disorders:

Very rare: reversible psychic disturbances including depression, anxiety disorders, agitation, confusion and hallucinations, reduced libido, insomnia

Hematologic:

Very rare: pancytopenia, leucopenia; thrombocytopenia, agranulocytosis, neutropenia.

Reproductive system and breast disorders:

Rare: impotence, reversible gynaecomastia

Cardic disorders:

Very rare: A-V block, interstitial pneumonia.

The adverse reactions in overdose cases are similar to the adverse reactions encountered in normal clinical experience (see section 4.8).

Patients with Zollinger-Ellison syndrome have tolerated doses up to 800 mg daily for more than a year without the development of significant adverse effects.

The usual measures to remove unabsorbed material from the gastrointestinal tract, clinical monitoring, and supportive therapy should be employed.

'Pepcid', in single oral doses of 5 mg to 40 mg, produced dose-related inhibition of basal and pentagastrin, betazole, or insulin-stimulated gastric secretion in healthy volunteers. The inhibition affected volume, acid, and pepsin content of the gastric juice. In patients with benign gastric or duodenal ulceration, similar inhibitory effects on gastric secretion were noted.

In volunteers given a second pentagastrin challenge 5-7 hours after the dose of 'Pepcid' the inhibition of gastric secretion persisted, in contrast to control subjects on cimetidine 300 mg or on placebo.

A single oral dose of 40 mg of 'Pepcid' given at 9 pm was effective for more than 12 hours after administration. The 40 mg dose also had some continuing effect through the breakfast meal. The 80 mg dose of 'Pepcid' administered at 9 pm had no longer duration of action than the 40 mg dose.

Basal serum gastrin levels were increased by 20 mg and 10 mg doses of 'Pepcid' in some studies but unchanged in others. Gastric emptying was not affected by 'Pepcid', nor were hepatic and portal blood flows altered. 'Pepcid' did not cause changes in endocrine function.

'Pepcid' obeys linear kinetics. 'Pepcid' is rapidly absorbed, with doserelated peak plasma concentrations reached in one to three hours. Bioavailability is not affected by the presence of food in the stomach. Repeated doses do not lead to accumulation of the drug.

Protein binding in the plasma is relatively low (15-20%). The plasma half-life after a single oral dose or multiple repeated doses (for 5 days) was approximately 3 hours.

Metabolism of the drug occurs in the liver, with formation of the inactive sulphoxide metabolite.

Approximately 25-60% of the oral dosage is excreted in the urine, mainly as unchanged drug. A small amount may be excreted as the sulphoxide.

No relevant information.

Magnesium Stearate (E572)

Microcrystalline Cellulose (E460)

Pregelatinised Starch

Talc

Hydroxypropyl Cellulose (E463)

Hypromellose (E464)

Red Iron Oxide (E172)

Titanium Dioxide (E171)

Yellow Iron Oxide (E172)

Carnauba Wax (E903)

None.

24 months.

Do not store above 25°C.

Opacified PVC-aluminium blister packs of 2 and 4 tablets and calendar packs of 28 tablets.

Amber glass, high density polyethylene or polypropylene bottles of 50 tablets.

None.

Merck Sharp & Dohme Limited

Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, UK.

20 mg tablet: PL 0025/0215

40 mg tablet: PL 0025/0216

Date granted: 8 September 1987

Last Renewed: 5 June 2008

01 May 2009

POM

® denotes registered trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA

© Merck Sharp & Dohme Limited 2009. All rights reserved.

SPC.PCD.08.UK.3001