Famotidine 40mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT
Famotidine 40mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains famotidine 40 mg.
Excipient with known effect: Each tablet contains 3.19mg of lactose (as lactose monohydrate).
For the full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Film-coated tablet
White, oblong, biconvex tablet, scored 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
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
Posology
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 48 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 10ml/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.
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.
Paediatric population: Not recommended.
Method 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 the active substance or to any of the excipients listed in section 6.1.
Cross sensitivity in 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.
For administration to breast-feeding women: see section 4.6
4.4 Special warnings and precautions for use
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.
Gastric neoplasm
Before starting treatment of gastric ulcer with famotidine, the possibility of malignant gastric tumour should be excluded. The symptomatic response of a gastric ulcer to famotidine therapy does not exclude the possible existence of a malignant tumour.
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 insufficiency.
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 10 ml/min (see section 4.2 Posology and Method of administration).
This medicine contains 1.99 mg of lactose monohydrate per tablet. Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Paediatric population
In the children are not established safety and efficacy.
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.
4.5 Interaction with other medicinal products and other forms of interaction
No drug interactions of clinical importance have been identified.
During concomitant use of drugs where the absorption of the drug is affected by the amount of gastric juice, a possible effect on the absorption should be taken into consideration. The absorption of ketoconazole and itraconazole could be reduced. Ketoconazole should be given two hours before famotidine administration.
Probenecid inhibits renal tubular secretion of famotidine, and has been shown to cause a 50% increase in plasma levels of famotidine. Therefore, concomitant use of probenecid and famotidine should be avoided.
Concomitant use of famotidine and antacids could reduce the famotidine uptake and cause lower plasma levels of famotidine. Therefore, famotidine should be administered 1-2 hours before antacids.
Concomitant use of sucralfate inhibits absorption of famotidine. Therefore, sucralfate should not be administered within 2 hours after famotidine.
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.
Alterations of gastric pH may affect the bioavailability of certain drugs resulting in a decrease in the absorption of atazanavir.
4.6 Fertility, pregnancy and lactation
Pregnancy:
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.
To date, no other relevant epidemiological data are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal / foetal development, parturition or postnatal development (see section 5.3).
Breast-feeding:
Famotidine is excreted in breast milk. Breast-feeding mothers should either stop using this drug or stop breast-feeding, since there is a possibility of famotidine affecting the infant’s gastric acid secretion.
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 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)]
Blood and the lymphatic system disorders
Very rare
Thrombocytopenia
Leukopenia
Agranulocytosis
Pancytopenia
neutropenia
Psychiatric disorders
Very rare
Reversible psychic disturbances including Hallucinations
Disorientation
Confusion
Anxiety disorders
Agitation
Depression
Reduced libido
Insomnia.
Nervous system disorders
Common
Headache
Dizziness
Uncommon: taste disorder
Very rare
Paraesthesia
Somnolence
Epileptic seizures, convulsions; grand mal seizures (particularly in patients with impaired renal function);
Gastrointestinal disorders
Common
Constipation
Diarrhoea
Uncommon
Nausea
Vomiting
Abdominal discomfort or distension
Flatulence
Dry mouth
Hepato-biliary disorders
Rare
Intrahepatic cholestasis (visible sign: jaundice),
Very rare
Hepatitis; cholestatic jaundice, Increase in liver enzyme abnormalities (transaminases, gamma GT, alkaline phosphatase, bilirubin)
Metabolism and nutrition disorders
Uncommon
Loss of appetite (anorexia)
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 (angioneurotic oedema, anaphylaxis, bronchospasm)
Respiratory, thoracic and mediastinal disorders
Very rare
Interstitial pneumonia sometimes fatal
Muscoskeletal, connective tissue and bone disorders
Very rare
Muscle cramps, Arthralgia
Cardiac disorders:
Very rare
AV block with H2 receptor antagonists administered intravenously
General disorders and administration site conditions:
Uncommon: fatigue Very rare: chest tightness
Reproductive system and breast disorders:
Very rare: impotence
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.
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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
4.9 Overdose
The adverse reactions in overdose cases are similar to the adverse reactions encountered in normal clinical experience (see Side Effects).
No cases of overdose have been reported so far.
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 with the usual measures from the gastrointestinal tract, clinical monitoring, and supportive therapy should be employed.
5 PHARMACOLOGICAL PROPERTIES
ATC code: A02B A03
Pharmacotherapeutic group: Histamine H2 receptor antagonist.
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 night-time 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
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.
The binding of famotidine in plasma proteins is relatively small (15-20%). The plasma half-life is about 3 hours both after oral single doses and during repeated administration (5 days).
Biotransformation
Up to 30-35 % of famotidine is metabolised in the liver to an inactive sulfoxide metabolite.
Elimination
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 30ml/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
Non clinical 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
Not applicable
6.3 Shelf life
3 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
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 and other handling
No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Tillomed Laboratories Ltd 3 Howard Road Eaton Socon St. Neots
Cambridgeshire PE19 8ET
8 MARKETING AUTHORISATION NUMBER(S)
PL 11311/0478
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 12/8/2009
10 DATE OF REVISION OF THE TEXT
14/09/2016