Famotidine 20mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Famotidine 20 mg Film Coated Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Famotidine 40 mg
Excipient with known effect: Each tablet contains 3.12 mg lactose.
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Film Coated Tablet
White, film coated, D shaped, biconvex tablets marked with ‘G’ on one side and ‘FD/20’ on the other side.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Famotidine tablets are indicated for the following conditions;
Duodenal ulcers
Prevention of relapses of duodenal ulceration Benign gastric ulcers Zollinger-Ellison syndrome and the Symptomatic treatment of mild reflux oesophagitis.
4.2 Posology and method of administration
Famotidine tablets are for oral use only.
The bioavailability of this product is not affected by the presence of food in the stomach, therefore it is not necessary to time the dose in relation to meals. In all cases, however the patients’ response should be taken into consideration.
Duodenal Ulcers — The initial recommended dose is 40mg of Famotidine to be taken at night. Healing generally occurs in most patients within 4 weeks. This period, however, may be shortened if an endoscopic examination reveals that the ulcer has healed. However, in those patients whose ulcers have not healed within this 4 week period, treatment should continue for a further 4 weeks.
Prevention of relapses of duodenal ulceration — To prevent ulcers from reoccurring the recommended dose is 20mg of Famotidine to be taken at night.
Benign gastric ulcers — The recommended dose of 40mg of Famotidine to be taken at night. Treatment should continue for between 4-8 weeks unless earlier healing is revealed by endoscopy.
Zollinger Ellison syndrome — Patients who are not receiving any antisecretory therapy should be started on a dose of 20mg of Famotidine every 6 hours. The dosage should then be adjusted to individual response.
If the desired inhibition of acid secretion cannot be attained with a daily dosage of 800mg, alternative treatment should be considered to regulate acid secretion, since no long term experience with dosages of more than 800mg of famotidine/day have been recorded.
Treatment should be continued for as long as necessary. Patients who have been receiving other H2 receptor antagonist treatment can begin famotidine treatment at a higher dosage than the initial dosage that is usually recommended. The starting dosage will depend on the severity of the disease and the dosage of the last dose of H2-antagonist previously used.
Symptomatic treatment of mild reflux oesophagitis - Recommended dosage is 20mg twice daily. Generally, treatment should be conducted for 6 weeks, if necessary for 12 weeks.
Elderly
The dosage regimen recommended for the elderly is the same as for adults.
Use in impaired renal function.
Famotidine is primarily eliminated via the kidneys. For patients with impaired renal function in whom creatinine clearance is less than 30mL/min, the daily dosage of famotidine should be reduced by 50%. Caution is advised in patients with renal impairment.
Dialysis patients should also take dosages that are reduced by 50%.
Famotidine 20mg tablets should be administered at the end of dialysis or thereafter since some of the active ingredient is removed via dialysis.
Famotidine tablets are not recommended for use in children.
4.3 Contraindications
Hypersensitivity to the active substance, to any of the excipients listed in section 6.1 or to other H2-receptor antagonists.
Cross sensitivity to this class of compounds has been observed. Therefore, famotidine 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
The presence of gastric malignancy should be excluded prior to the use of Famotidine tablets for the treatment of gastric ulcers. Symptomatic responses of gastric ulcers following treatment with Famotidine do not preclude the presence of gastric malignancy.
RENAL DYSFUNCTION
As Famotidine is excreted primarily via the kidneys, caution should be exercised when treating patients who are suffering from impaired renal function. A reduction in daily dosage should be considered if creatinine clearance falls below 10 ml/min. For dosage regimes refer to the posology section.
PEDIATRIC USE
The safety and efficacy for the use of Famotidine tablets in children has not been established.
USE IN THE ELDERLY
When Famotidine 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
This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
No clinically important drug interactions have been identified.
Famotidine does not appear to interact with the cytochrome P450 drug metabolising enzyme system. Compunds metabolised by this system, which have been tested in man have included warfarin, theophylline, phenytoin, diazepam, propranolol, aminopyrine and antipyrine.
Indocyanide 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.
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.
Probenicid inhibits the renal tubular secretion of famotidine and has been shown to cause a 50% increase in famotidine plasma concentrations.
Therefore concomitant use of probenecid and famotidine should be avoided.
Concomitant use of famotidine and antacids can reduce the famotidine absorption and lead to lower plasma levels of famotidine. Therefore, famotidine should be administered 1-2 hours before taking an antacid.
Concomitant use of sucralfate inhibits the absorption of famotidine. Therefore, sucralfate should as a rule not be administered within two hours of the famotidine dose.
4.6 Fertility, pregnancy and lactation
Pregnancy:
Famotidine tablets are not recommended for use in pregnancy, and should be prescribed only if clearly needed. Before a decision is made to use famotidine tablets during pregnancy, the physician should weigh the potential benefits from the drug against the possible risks involved.
Breast-feeding:
Famotidine is secreted in human breast milk. Therefore breast feeding mothers should either stop taking Famotidine or stop breast feeding.
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).
4.8 Undesirable effects
Famotidine tablets have been demonstrated to be generally well-tolerated.
Adverse reactions are ranked under the heading of frequency, the most frequent first, using the following convention: very common (> 1/10), common (> 1/100, < 1/10), uncommon (> 1/1000, < 1/100), rare (> 1/10,000,
< 1/1000), very rare (< 1/10,000), including isolated cases. Not known (cannot be estimated from the available data).
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Blood and Lymphatic system disorders Very rare |
Thrombocytopenia, leucopenia, agranulocytosis, pancytopenia, neutropenia. |
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Immune system disorders | |
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Very rare |
Hypersensitivity reactions (anaphylaxis, angioneurotic oedema, bronchospasm). |
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Psychiatric disorders | |
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Very rare |
Reversible psychological disturbances including hallucinations, disorientation, confusion, anxiety disorders, agitation, depression, insomnia, reduced libido. |
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Nervous system disorders | |
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Common |
Headache, dizziness. |
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Uncommon |
Fatigue, taste disorder. |
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Very rare |
Paraesthesia, drowsiness, convulsions, grand mal seizures (particularly in patients with impaired renal function). |
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Metabolism and nutrition disorders Uncommon |
Anorexia. |
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Gastrointestinal disorders Common |
Constipation, diarrhoea. |
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Uncommon |
Dry mouth, nausea and/or vomiting, anorexia, flatulence, abdominal discomfort or distension. |
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Hepatobiliary disorders Very rare |
Liver enzyme abnormalities, hepatitis, cholestatic jaundice. Isolated cases of worsening of existing hepatic disease. |
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Skin and subcutaneous tissue disorders Uncommon |
Rash, pruritus, urticaria. |
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Very rare |
Alopecia, Stevens-Johnson Syndrome/toxic epidermal necrolysis sometimes fatal. |
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Musculoskeletal, connective tissue and bone disorders Very rare |
Arthralgia, muscle cramps. |
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Reproductive system and breast disorders Very rare |
Impotence. |
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Cardiac disorders Very rare |
Atrioventricular block with H2-receptor antagonists administered intravenously, arrhythmias, chest tightness. |
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Respiratory, thoracic and mediastinal disorders |
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Very rare |
Interstitial pneumonia, sometimes fatal. |
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Investigations | |
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Rare |
Increase in laboratory values (transaminases, gamma GT, alkaline phosphatase, bilirubin). |
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Very rare |
QT Prolongation. |
Adverse Effects - Casual Relationship Unknown
Rare cases of gynaecomastia have been reported, however, in controlled
clinical trials the incidences were not greater that those seen with placebo.
4.9 Overdose
The adverse reactions in overdose cases are similar to the adverse reactions encountered in normal clinical experiences (see Side Effects).
In the event of overdose the usual measures should be employed to remove unabsorbed material from the gastrointestinal tract, clinical monitoring and supportive therapy should be employed.
Patients suffering from Zollinger-Ellison syndrome have tolerated doses of up to 800 mg/day. These patients have been treated for more than a year without the development of any significant adverse effects.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
ATC code: A02B A03
Pharmacotherapeutic group: H2-receptor antagonists
In healthy volunteers, single oral doses of famotidine (5 mg to 40 mg), produced dose-related inhibition of basal and pentagastrin, betazole or insulin-stimulated gastric secretion . In addition, pepsin levels were also reduced and there was a decrease in the volume of the basal gastric juice and the gastric juice secreted on stimulation. Similar inhibitory effects on gastric secretion were also noted in patients with benign gastric or duodenal ulceration.
In contrast to control subjects on cimetidine 300 mg or on placebo, inhibition of gastric secretion persisted in volunteers given a second pentagastrin challenge 5-7 hours after the initial dose of famotidine.
A single oral dose of 40 mg of famotidine, given at 9 pm was effective for more than 12 hours after administration and had some continuing effect through the breakfast meal. The duration of action of the 80 mg dose of famotidine administered at 9 pm was no longer than the 40 mg dose.
In several studies, 10 mg and 20 mg doses of famotidine increased basal serum gastrin levels, however the levels remained unchanged in others. Gastric emptying, and hepatic and portal blood flows were unaltered by famotidine. In addition, famotidine did not cause changes in endocrine function.
5.2 Pharmacokinetic properties
Famotidine displays linear kinetics. The drug is rapidly absorbed and takes effect within an hour of oral administration, reaching dose-related peak plasma concentrations within 1-3 hours. Oral bioavailability is not affected by the presence of food in the stomach. Repeat doses do not lead to accumulation of the drug.
There is relatively low (15-20%) protein binding of famotidine in the plasma. The plasma half-life after a single oral dose or multiple repeated doses (for 5 days) is approximately 3 hours.
The drug is metabolised in the liver to inactive sulphoxide metabolites. Famotidine is excreted mainly unchanged in the urine (25-60%); a small amount of the drug may be excreted as the sulphoxide.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber, which are additional to that already included in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Cellulose, microcrystalline Starch, pregelatinised Talc
Magnesium stearate Film-coating:
Opadry II White Y30-18037 containing:
Lactose monohydrate Hydroxypropylmethylcellulose Titanium dioxide (E171)
Triacetin
Not applicable
6.3 Shelf life
2 years.
6.4 Special precautions for storage
Do not store above 25°C. Store in the original package.
6.5 Nature and contents of container
Polyvinylchloride aluminium foil blisters packed into cartons containing 10, 20, 28, 30, 50, 56, 60, 90 or 100 tablets. Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
No special requirements
7 MARKETING AUTHORISATION HOLDER
Generics [UK] Limited t/a Mylan
Station Close
Potters Bar
Hertfordshire
EN6 1TL
United Kingdom
8. MARKETING AUTHORISATION NUMBER(S)
PL 04569/0422
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 2 July 2001 Date of last renewal: 2 July 2006
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DATE OF REVISION OF THE TEXT
02/07/2006