Famotidine 20mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Famotidine 20 mg film-coated tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
One film-coated tablet contains 20 mg famotidine.
Excipients: Lactose monohydrate
One film-coated tablet contains 1,99 mg lactose monohydrate.
For a full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Film-coated tablet
White, oblong, biconvex tablet, scored on one side The tablet can be divided into equal halves.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Duodenal and benign gastric ulcers which have been confirmed by radiological or endoscopic examination.
Zollinger-Ellison syndrome
Reflux oesophagitis confirmed by endoscopy, including curative treatment of erosion or ulcer associated with reflux oesophagitis.
4.2 Posology and method of administration
Use in adults Duodenal ulcer.
Initiation of treatment: The recommended dose is 40 mg of famotidine per day at bedtime. The treatment should be continued for 4-8 weeks, but it may be discontinued even earlier if it is found by endoscopic examination that the ulcer has healed. In most cases the ulcer will heal with this treatment within four weeks. Treatment should be continued for another four weeks in patients whose ulcer has not healed completely within four weeks.
Maintenance treatment: In prophylactic treatment of recurrent ulcer it is recommended that famotidine therapy be continued with a dose of 20 mg per day at bedtime.
Non-malignant gastric ulcer.
The recommended dose is 40 mg per day at bedtime. The treatment is continued for 4-8 weeks, but a shorter course of treatment is adequate if an endoscopic examination shows that the ulcer is healed.
Zollinger-Ellison syndrome
If the patient has not previously received drugs to reduce the secretion of acid, the treatment is introduced by giving 20 mg of famotidine every 6 hours. The dosage should be adjusted according to the patient's needs and it should be continued as long as it is clinically indicated. Daily doses up to 800 mg have been administered without any significant undesirable effects or tachyphylaxis. If the patient has received another H2 blocking agent, famotidine therapy can be introduced in a larger dose than otherwise recommended. The size of the initial dose is dependent on the severity of the condition and on the size of doses of H2 blocking agents received until that time.
Reflux oesophagitis.
The recommended dose for the relief of symptoms of reflux oesophagitis is 20 mg of famotidine twice daily. Doses should be continued for as long as indicated.
The recommended dose for the treatment of erosion or ulcer associated with reflux oesophagitis is 40 mg of famotidine twice daily. The recommended treatment length is 6-8 weeks.
Maintenance treatment:
If long-term management of reflux oesophagitis by famotidine is considered relevant, the recommended dose is 20 mg twice daily.
At present, this prophylactic treatment is not recommended to be extended beyond six months.
Renal impairment
Famotidine is primarily eliminated via the kidneys. For patients with impaired renal function in whom creatinine clearance is less than 30ml/min, the daily dose of famotidine should be reduced by 50%. Caution is advised in patients with renal impairment. Dialysis patients should also take doses that are reduced by 50%. Famotidine tablets should be administered at the end of dialysis or later since some of the active ingredient is removed by dialysis.
Hepatic impairment
In patients with cirrhosis of the liver, the plasma concentration and elimination of famotidine in the urine were the same as that of healthy volunteers. Reduction of the dose is therefore not necessary in these patients.
Use in the elderly
When famotidine was administered to elderly patients in clinical studies the undesirable effects associated with the drug were not found to increase nor were they found to be different from those exhibited in younger patients. Adjustment of dose based on age is therefore not necessary.
Use in children Not recommended.
Mode of administration
The tablets should be taken with some liquid. They can be divided, but they must not be crushed or chewed.
4.3 Contraindications
- Hypersensitivity to famotidine or to any of the excipients.
Since cross sensitivity has been observed among H2-receptor antagonists,
famotidine should not be administered to patients with a history of hypersensitivity to other drugs in this class.
4.4 Special warnings and precautions for use Gastric neoplasm
Gastric malignancy should be excluded prior to initiation of therapy of gastric ulcer with famotidine. Symptomatic response of gastric ulcer to famotidine therapy does not preclude the presence of gastric malignancy.
Do not administer famotidine tablets in cases of minor gastro-intestinal complaints.
In patients with duodenal ulcers and benign gastric ulcers the H. Pylori status should be determined. Wherever possible, patients with H. Pylori should undergo eradication therapy to eliminate the bacteria.
Renal dysfunction
Since famotidine is secreted mainly via the kidneys, caution should be exercised when treating patients with renal insufficiency. A reduction in the daily dose should be considered if creatinine clearance falls below 30 ml/min (see section 4.2).
Paediatric population
The safety and efficacy of Famotidine 20 mg film-coated tablets in children has not yet 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.
Excipients
This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsoprtion should not take this medicine.
4.5 Interaction with other medicinal products and other forms of
interaction
No drug interactions of clinical importance have been identified.
Famotidine does not interact with the cytochrome P450-linked drug metabolizing enzyme system. Compounds metabolized 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 stabilized 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.
Ketoconazole and itraconazole (drugs with pH-dependend absorption)
The absorption of ketoconazole and itraconazole could be reduced. Ketoconazole or itraconazole should be given two hours before famotidine administration.
Atazanavir
Alterations of gastric pH may affect the bioavailability of certain drugs resulting in a decrease in the absorption of atazanavir.
Probenecid
The administration of probenecid can delay the elimination of famotidine. Concomitant use of probenecid and famotidine should be avoided.
Antacids
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.
Sucralfate
The concomitant use of sucralfate should be avoided within 2 hours of the famotidine dose
4.6 Fertility, pregnancy and lactation
Famotidine is not recommended for use in pregnancy, and should be prescribed only if clearly needed. Before a decision is made to use Famotidine during pregnancy, the physician should weigh the potential benefits from the drug against the possible risks involved.
Famotidine is detectable in human milk. Nursing mothers should either stop this drug or stop nursing.
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
The frequencies of adverse events are ranked according to the following: 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), not known (cannot be estimated form the available data).
Blood and the lymphatic system disorders
Very rare: thrombocytopenia, leukopenia, agranulocytosis, pancytopenia, neutropenia
Immune system disorders
Very rare: hypersensitivity reactions (angioneurotic oedema, anaphylaxis, bronchospasm)
Metabolism and nutrition disorders
Uncommon: anorexia
Psychiatric disorders
Very rare: reversible psychic disturbances including hallucinations,
disorientation, confusion, anxiety disorders, agitation, depression
Nervous system disorders
Common: headache, dizziness
Very rare: paraesthesia, somnolence, insomnia, convulsions, gran mal
seizures (particularly in patients with impaired renal function)
Cardiac disorders
Very rare: AV- block, when H2-receptor antagonists have been administered intravenously
Respiratory, thoracic and mediastinal disorders
Very rare: chest tightness, interstitial pneumonia sometimes fatal
Gastrointestinal disorders
Common: constipation, diarrhoea
Uncommon: nausea, vomiting, abdominal discomfort or distension, flatulence, dry mouth, dysgeusia
Hepato-biliary disorders
Very rare: increase in liver enzyme abnormalities (transaminases, gamma GT, alkaline phosphatase, bilirubin), intrahepatic cholestasis (visible sign: jaundice), hepatitis
Skin and subcutaneous tissue disorders
Uncommon: rash, pruritus, urticaria
Very rare: alopecia, severe skin reactions (Stevens Johnson Syndrom/toxic epidermal necrolysis sometimes fatal)
Musculoskeletal, connective tissue and bone disorders
Very rare: arthralgia, muscle cramps
Reproductive system and breast disorders
Very rare: impotence, reduced libido
General disorders and administration site conditions
Uncommon: fatigue
Adverse Effects - Causal Relationship Unknown
Rare cases of gynecomastia, 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 suffering from Zollinger-Ellison syndrome have received daily doses of up to 800 mg over a period of one year without exhibiting any significant undesirable effects.
In the event of overdose the aim should be to remove any unabsorbed drug from the alimentary tract. The patient should be monitored and should be given supporting treatment.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group. Histamine H2 receptor antagonist.
ATC code: A02B A03
Famotidine is an effective competitive H2 receptor antagonist, the effect of which is particularly clearly concentrated on H2 receptors. It reduces the concentration and amount of acid and pepsin of the gastric juices in the basal and stimulated secretion.
The effect of oral administration of famotidine is rapid. The effect of famotidine is long lasting when recommended doses are used, and it is effective with relatively low concentrations in the blood. The duration of effect, plasma concentration and secretion in the urine are dose dependent.
Oral administration of famotidine leads to the antacid effect starting within an hour of administration. The peak effect is dose dependent and it is achieved within 1-3 hours of administration.
In clinical studies famotidine was found to relieve the pain associated with ulceration, usually during the first week of treatment, and it reduced the gastric acid secretion with one single daily dose at bedtime.
Individual oral doses of 20mg and 40mg effectively inhibited the basal nighttime secretion of gastric acid; mean gastric acid secretion was inhibited over a period of 10 hours by 86% and 94%, respectively. The same doses, administered in the morning, inhibited the gastric acid secretion stimulated by eating for 3-5 hours p.a. by a mean of 76% and 84%, respectively. 8-10 hours after administration, the levels were at 25% and 30%, respectively, although the effect of one 20mg dose persisted for only 6-8 hours in some of the volunteers.
The basal night-time intragastric pH value was increased to a mean of 5 and 6.4 by evening doses of 20mg and 40mg of famotidine, respectively. When famotidine was administered after breakfast, the pH value in both the 20mg and the 40mg groups was increased to approximately 5 after 3 and 8 hours.
5.2 Pharmacokinetic properties
Oral administration.
Absorption.
Famotidine is rapidly absorbed. Peak plasma concentration is dose dependent and is achieved within 1-3 hours of administration. The kinetics of famotidine are linear. The bioavailability of oral famotidine is 40-45% on average. Food contained in the stomach will not affect the bioavailability. First pass metabolism of famotidine is minor. Repeat administration will not cause accumulation of the drug in the body.
Distribution in the body.
The binding of famotidine in plasma proteins is relatively small (1520%). The plasma half-life is about 3 hours both after oral single doses and during repeated administration (5 days).
Metabolism.
Up to 30-35 % of famotidine is metabolised in the liver to an inactive sulfoxide metabolite.
Excretion from the body.
When administered orally, an average of 65-70% of the absorbed famotidine is excreted in the urine. About 25-30% of the total oral dose is excreted unchanged in the urine. The renal clearance of famotidine is 250-450 ml/min, so consequently, excretion also takes place through tubular secretion. A small proportion may be secreted as sulfoxide.
Pharmacokinetics in different patient groups.
The average elimination half-life of famotidine in plasma was prolonged to 11.7 hours in patients with creatinine clearance of 30 ml/min or less. Patients with maximum creatinine clearance of 10 ml/min had an average plasma half-life of approximately 13 hours. The elimination half-life in these patients may exceed 20 hours. In patients with anuria the elimination half-life was prolonged to about 24 hours. In patients with creatinine clearance of 30 ml/min or less, only 21.2% of the intravenous injection was excreted in the urine.
In men with liver cirrhosis, famotidine plasma concentration and excretion of famotidine in the urine were of the same degree as in healthy trial subjects.
Disturbance of liver function apparently has no effect on the pharmacokinetics of famotidine.
Pharmacokinetic studies on elderly patients showed no signs of any clinically significant age-related changes; however, age-related impairment of renal function should be considered when determining the dose.
5.3 Preclinical safety data
Preclinical data on famotidine reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and toxicity to reproduction.
6. PHARMACEUTICAL PARTICULARS
6.1. List of excipients
Cellulose, microcrystalline. Lactose monohydrate. Macrogol 4000. Magnesium stearate. Hypromellose. Sodium starch glycolate (type A). Silica, colloidal anhydrous.
Pregelatanized starch. Talc. Titanium dioxide (E 171).
6.2. Incompatibilities
None applicable
Shelf life
6.3.
4 years
6.4. Special precautions for storage
Do not store above 25°C.
Store in the original packaging. Keep the blister in the outer carton.
6.5. Nature and contents of container
The tablets are packed in Al/PVC blisters which are inserted into a carton folder.
The following sizes of original packages are available:
5, 7, 10, 14, 15, 20, 28, 30, 49, 50, 56, 60, 90, 98, 100 film-coated tablets
Not all pack sizes may be marketed
6.6 Special precautions for disposal
No special requirements.
7. MARKETING AUTHORISATION HOLDER
Tillomed Laboratories Ltd
3 Howard Road
Eaton Socon
St. Neots
Cambridgeshire
PE19 8ET
United Kingdom
8. MARKETING AUTHORISATION NUMBER
PL 11311/0226
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
06/05/2007
10 DATE OF REVISION OF THE TEXT
16/07/2010