1.1  Therapeutic indications

Duodenal ulcers and prevention of relapses of duodenal ulceration. Benign gastric ulcers.

Zollinger-Ellison syndrome.

Symptomatic treatment of mild to moderate reflux oesophagitis.

1.1  Posology

Adults

Duodenal ulcers - The initial recommended dose is 40 mg of famotidine to be taken at night. Healing generally occursin most patients within 4 weeks. This period, however, may be shortened if an endoscopic examination reveals that theulcer has healed. However, in those patients whose ulcers have not healed within this 4 week period, treatment shouldcontinue for a further 4 weeks.

Prevention of relapses of duodenal ulceration - To prevent ulcers from reoccurring the recommended dose is 20 mg offamotidine to be taken at night.

Benign gastric ulcers - The recommended dose of 40 mg of famotidine to be taken at night. Treatment should continuefor 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. Doses up to 800 mg dailyhave been used up to one year without the development of significant adverse effects or tachyphylaxis.

If the desired inhibition of acid secretion cannot be attained with a daily dosage of 800 mg, alternative treatment shouldbe considered to regulate acid secretion, since no long term experience with dosages of more than 800 mg offamotidine/day have been recorded.

Treatment should be continued for as long as necessary. Patients who have been receiving other H-receptorantagonist treatment may be switched directly to famotidine treatment at a higher dosage than the initial dosage that isusually recommended. The starting dosage will depend on the severity of the condition and the size of the last dose ofH-antagonist previously used.

Symptomatic treatment of mild to moderate oesophagitis - The recommended dose in case of mild oesophagitis is 20mg of famotidine twice daily. In case of mild to moderate oesophagitis, the recommended dose is 40 mg twice daily.Generally treatment should be conducted for 6 weeks. If the condition has not improved, treatment should be continuedfor a further 6 weeks.

Renal impairment:

Famotidine is primarily eliminated via the kidneys. For patients with impaired renal function in whom creatinineclearance is less than 30 ml/min, the daily dose of famotidine should be reduced by 50%. Caution is advised inpatients with renal impairment.

Dialysis patients should also take dosages that are reduced by 50%. Famotidine 20 mg tablets should be administeredat the end of dialysis or thereafter since some of the active ingredient is removed by dialysis.

Elderly:

The dosage regimen recommended for elderly patients is the same as for adults. Paediatric population:

The efficacy and safety of famotidine in children have not been established. Method of administration

For oral use.

Famotidine tablets can be taken with or without food (see section 5.2).

Gastric neoplasm

The presence of gastric malignanncy should be excluded prior to the use of famotidine for the treatment of gastriculcers. Symptomatic responses of gastric ulcers following treatment with famotidine do not preclude the presence ofgastric malignancy.

Renal insufficiency

As famotidine is excreted primarily via the kidneys, caution should be exercised when treating patients who aresuffering from impaired renal function. A reduction in the daily dose to 20 mg at night should be considered if creatinineclearance falls below 10 ml/min (see section 4.2).

Paediatric population

The safety and efficacy for the use of Famotidine 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.

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose galactose malabsorption should not take this medicine

No clinically important drug interactions have been identified.

Famotidine does not interact with the cytochrome P450 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.

Indocyanide green as an index of hepatic blood flow and/or hepatic drug extraction has been tested and no significanteffects have been found.

Studies in patients stabilised on phenprocoumon therapy have shown no pharmacokinetic interaction with famotidineand 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 alcoholingestion.

lterations of gastric pH may affect the bioavailability of certain drugs, resulting in a decrease in the absorption ofatazanavir. The absorption of ketoconazole and itraconazole could be reduced. Ketoconazole should be administeredtwo hours before famotidine.

Probenecid inhibits the renal tubular secretion of famotidine and has been shown to cause a 50% increase infamotidine plasma concentrations. Therefore, concomitant use of probenecid and famotidine should be avoided.

Concomitant use of famotidine and antacids could reduce the famotidine absorption and lead to lower plasma levels offamotidine. Therefore, famotidine should be administered 1-2 hours before taking an antacid.

Concomitant use of sucralfate inhibits the absorption of famotidine. Therefore, sucralfate should not be administeredwithin 2 hours of the famotidine dose.

Risk of loss of efficacy of calcium carbonate when co-administered as phosphate binder with famotidine inhaemodialysis patients.

Pregnancy:

Famotidine is not recommended for use in pregnancy, and should be prescribed only if clearly needed. Before adecision is made to use famotidine during pregnancy, the physician should weigh the potential benefits from the drugagainst the possible risks involved.

Breast-feeding:

Famotidine is excreted in human breast milk. Therefore breast-feeding mothers should either stop taking famotidine orstop breast-feeding.

Some patients have experienced adverse reactions such as dizziness and headache while taking famotidine. Patientsshould be informed that they should avoid driving vehicles or operating machinery or doing activities which requireprompt vigilance if they experience these symptoms (see section 4.8).

Famotidine has 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, <1/1,000), VeryRare (<1/10,000), including isolated cases not known (cannot be estimated from the available data).

Blood and 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

Loss of appetite (anorexia) Psychiatric disorders

Very rare

Reversible psychological 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 Convulsions

Grand mal seizures (particularly in patients with impaired renal function) Cardiac disorders

Very rare

AV block with H-receptor antagonists administered intravenously Arrhythmias

QT prolongation (especially in patients with impaired renal function) Respiratory, thoracic and mediastinal disorders

Very rare

Interstitial pneumonia, sometimes fatal Gastrointestinal disorders

Common Constipation Diarrhoea Uncommon

Nausea and or vomiting

Abdominal discomfort or distension Flatulence

Dry mouth

Hepato-biliary disorders Very rare

Hepatitis Cholestatic jaundice

Liver enzyme abnormalities

Isolated cases of worsening of existing hepatic disease Skin and subcutaneous tissue disorders

Uncommon Rash Pruritus Urticaria Very rare

Alopecia

Stevens Johnson syndrome/toxic epidermal necrolysis sometimes fatal Muscoskeletal and connective tissue disorders

Very rare Muscle cramps Arthralgia

Reproductive system and breast disorders Very rare

Impotence

General disorders and administration site conditions Uncommon: fatigue

Very rare: chest tightness Investigations

Rare

Increase in laboratory values (transaminases, gamma GT, alkaline phosphatase, bilirubin). Adverse Effects - Causal Relationship Unknown

Rare cases of gynecomastia, have been reported, however, in controlled clinical trials the incidences were not greaterthan 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 (see details below)

Reporting of suspected adverse reactions

•  Saudi Arabia:

o Other GCC States:

Please contact the relevant competent authority.

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

In the event of overdose the usual measures to remove unabsorbed material from the gastrointestinal tract, clinicalmonitoring and supportive therapy should be employed.

Patients suffering from Zollinger-Ellison syndrome have tolerated doses of up to 800 mg/day. These patients have beentreated for more than a year without the development of any significant adverse effects.

ATC code: A02B A03

Pharmacotherapeutic group: Drugs for peptic ulcer and gastro-oesophageal reflux disease (GORD), H2 -receptorantagonists.

Clinical efficacy and safety

In healthy volunteers, single oral doses of famotidine (5 mg to 40 mg) produced dose related inhibition of basal andpentagastrin, betazole or insulin-stimulated gastric secretion. In addition, pepsin levels were also reduced and therewas 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 involunteers 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 andhad some continuing effect through the breakfast meal. The duration of action of the 80 mg dose of famotidineadministered 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 levelsremained unchanged in others. Gastric emptying, and hepatic and portal blood flows were unaltered by famotidine. Inaddition, famotidine did not cause changes in endocrine function.

Absorption.

Famotidine is rapidly absorbed and takes effect within an hour of oral administration, reaching dose-related peakplasma concentration 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.

Distribution.

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

Biotransformation

Famotidine is metabolised in the liver, with formation of the inactive sulfoxide metabolite. Elimination

Famotidine is excreted mainly unchanged in the urine (25-60%); a small amount of the drug may be excreted assulfoxide.

Linearity/non-linearity

Famotidine displays linear kinetics.

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in othersections of the SPC.

Peploc (Famotidine Tablets USP 10mg):

Microcrystalline Cellulose (Avicel-PH101), Corn Starch (Extra white maize Strach), Sodium Starch Glycolate Type A (Primojel), Hypromellose 2910 5cps (Methocel E5-LV Premium), Microcrystalline Cellulose (Avicel-PH102) and Magnesium stearate (Ligamed MF-2-V).

Film coating composition: Hypromellose 2910, Hydroxyl Propyl Cellulose, Titanium dioxide, Talc and Carnuba Wax.

Peploc (Famotidine Tablets USP 20mg):

Microcrystalline Cellulose (Avicel-PH101), Corn Starch (Extra white maize Strach), Sodium Starch Glycolate Type A (Primojel), Hypromellose 2910 5cps (Methocel E5-LV Premium), Microcrystalline Cellulose (Avicel-PH102) and Magnesium stearate (Ligamed MF-2-V).

Film coating composition: Hypromellose 2910, Hydroxyl Propyl Cellulose, Titanium dioxide, Talc, Carnuba Wax, Yellow Iron Oxide and Red Iron Oxide.

Peploc (Famotidine Tablets USP 40mg):

Microcrystalline Cellulose (Avicel-PH101), Corn Starch (Extra white maize Strach), Sodium Starch Glycolate Type A (Primojel), Hypromellose 2910 5cps (Methocel E5-LV Premium), Microcrystalline Cellulose (Avicel-PH102) and Magnesium stearate (Ligamed MF-2-V).

Film coating composition: Hypromellose 2910, Hydroxyl Propyl Cellulose, Titanium dioxide, Talc and Carnuba Wax.

NA

Store below 30ºC.

10’s Blister pack

NA