1. Name Of The Medicinal Product
PEPCID® 20 mg Tablets
PEPCID® 40 mg Tablets
2. Qualitative And Quantitative Composition
'Pepcid' 20 mg, each tablet contains 20 mg of famotidine.
'Pepcid' 40 mg, each tablet contains 40 mg of famotidine.
3. Pharmaceutical Form
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.
4. Clinical Particulars
4.1 Therapeutic Indications
Duodenal ulcer.
Prevention of relapses of duodenal ulceration.
Benign gastric ulcer.
Hypersecretory conditions such as Zollinger-Ellison syndrome.
Treatment of gastro-oesophageal reflux disease.
Prevention of relapse of symptoms and erosions or ulcerations associated with gastro-oesophageal reflux disease.
4.2 Posology And Method Of Administration
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 four-week 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.
Zollinger-Ellison 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.
Gastro-oesophageal reflux disease
The recommended dosage for the symptomatic relief of gastro-oesophageal 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 gastro-oesophageal 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' has not been established in children.
4.3 Contraindications
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.
4.4 Special Warnings And Precautions For Use
Gastric neoplasm
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.
Paediatric Use
In the children are not established safety and efficacy.
Use in the elderly
When 'Pepcid' was administered to elderly patients in clinical trials, no increase in the incidence or change in the type of drug-related side effects was observed. No dosage adjustment is required based on age alone.
General
In case of long-term treatment with high dosage, monitoring of blood count and liver function is recommended.
In case of long-standing ulcer disease, abrupt withdrawal after symptom relief should be avoided.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
No drug interactions of clinical importance have been identified.
'Pepcid' does not interact with the cytochrome P450-linked drug metabolising enzyme system. Compounds metabolised by this system which have been tested in man have included warfarin, theophylline, phenytoin, diazepam, propranolol, aminopyrine and antipyrine. Indocyanine green as an index of hepatic blood flow and/or hepatic drug extraction has been tested and no significant effects have been found.
Studies in patients stabilised on phenprocoumon therapy have shown no pharmacokinetic interaction with famotidine and no effect on the pharmacokinetic or anticoagulant activity of phenprocoumon.
In addition, studies with famotidine have shown no augmentation of expected blood alcohol levels resulting from alcohol ingestion.
Alterations of gastric pH may affect the bioavailability of certain drugs resulting in a decrease in the absorption of atazanavir.
The absorption of ketoconazole and itraconazole could be reduced. Ketoconazole should be given 2 hours before famotidine administration.
Antacids may decrease the absorption of famotidine and lead to lower plasma concentrations of famotidine. Famotidine should therefore be taken 1 - 2 hours before the application of an antacid.
The administration of probenecid can delay the elimination of famotidine. Concomitant use of probenecid and famotidine should be avoided.
The concomitant use of sucralfate should be avoided within two hours of the famotidine dose.
4.6 Pregnancy And Lactation
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.
Breast-feeding mothers: 'Pepcid' is secreted in human milk, therefore breast-feeding mothers should either stop breast-feeding or stop taking the drug.
4.7 Effects On Ability To Drive And Use Machines
Some patients have experienced adverse reactions such as dizziness and headache while taking famotidine. Patients should be informed that they should avoid driving vehicles or operating machinery or doing activities which require prompt vigilance if they experience these symptoms. (see 'section 4.8 Undesirable Effects').
4.8 Undesirable Effects
'Pepcid' has been demonstrated to be generally well-tolerated.
[Very Common (>1/10) Common (>1/100, <1/10) Uncommon (>1/1000, <1/100) Rare (>1/10,000, <1/1,000) Very rare (<1/10,000) including isolated cases Not known (cannot be estimated from the available data)]
Nervous system disorders:
Common: headache, dizziness
Uncommon: taste disorder
Very rare: convulsions, grand mal seizures (particularly in patients with impaired renal function), paraesthesia, somnolence
Respiratory, thoracic, and mediastinal disorders:
Very rare: interstitial pneumonia sometimes fatal
Gastro-intestinal disorders:
Common: constipation, diarrhoea
Uncommon: dry mouth, nausea and/or vomiting, abdominal discomfort or distension, flatulence
Metabolism and nutrition disorders:
Uncommon: anorexia
Hepatobiliary disorders:
Very rare: liver enzyme abnormalities, hepatitis, cholestatic jaundice
Skin and subcutaneous tissue disorders:
Uncommon: rash, pruritus, urticaria
Very rare: alopecia, Stevens Johnson Syndrome/toxic epidermal necrolysis sometimes fatal
Immune system disorders:
Very rare: hypersensitivity reactions (anaphylaxis, angioneurotic oedema, bronchospasm)
Musculoskeletal and connective tissue disorders:
Very rare: arthralgia, muscle cramps
General disorders and administration site conditions:
Uncommon: fatigue
Very rare: chest tightness
Psychiatric disorders:
Very rare: reversible psychic disturbances including depression, anxiety disorders, agitation, disorientation, confusion and hallucinations, reduced libido, insomnia
Blood and lymphatic disorders:
Very rare: pancytopenia, leucopenia, thrombocytopenia, agranulocytosis, neutropenia.
Reproductive system and breast disorders:
Very rare: impotence
Cardiac disorders:
Very rare: A-V block with H2 receptor antagonists administered intravenously, prolonged QT interval (particularly in patients with impaired renal function)
Adverse Effects – Causal Relationship Unknown
Rare cases of gynaecomastia, have been reported, however, in controlled clinical trials the incidences were not greater than those seen with placebo.
4.9 Overdose
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 gastro-intestinal tract, clinical monitoring, and supportive therapy should be employed.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
'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.
5.2 Pharmacokinetic Properties
'Pepcid' obeys linear kinetics. 'Pepcid' is rapidly absorbed, with dose-related 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.
5.3 Preclinical Safety Data
No relevant information.
6. Pharmaceutical Particulars
6.1 List Of Excipients
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)
6.2 Incompatibilities
None.
6.3 Shelf Life
24 months.
6.4 Special Precautions For Storage
Do not store above 25°C.
6.5 Nature And Contents Of Container
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.
6.6 Special Precautions For Disposal And Other Handling
None.
7. Marketing Authorisation Holder
Merck Sharp & Dohme Limited
Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, UK.
8. Marketing Authorisation Number(S)
20 mg tablet: PL 00025/0215
40 mg tablet: PL 00025/0216
9. Date Of First Authorisation/Renewal Of The Authorisation
Date granted: 8 September 1987
Last Renewed: 5 June 2008
10. Date Of Revision Of The Text
25 February 2011
11. LEGAL CATEGORY
POM
© Merck Sharp & Dohme Limited 2011. All rights reserved.
SPC.PCD.10.UK.3353
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