4.1. Therapeutic indications

Famotidine tablets are indicated for the following conditions;

- Prevention of relapses of duodenal ulceration

- Duodenal ulcers

- Benign gastric ulcers

- Zollinger-Ellison syndrome

- Symptomatic treatment of mild to moderate reflux oesophagitis

4.2. Posology and method of administration

Posology

Adults

Duodenal ulcers - The initial recommended dose is 40 mg 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 20 mg of famotidine to be taken at night

Benign gastric ulcers – The recommended dose of 40 mg 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 20 mg of famotidine every 6 hours. The 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.

If the desired inhibition of acid secretion cannot be attained with a daily dosage of 800 mg, alternative treatment should be considered to regulate acid secretion, since no long term experience with dosages of more than 800 mg 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 may be switched directly to 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 to moderate oesophagitis – The recommended dose in case of mild oesophagitis is 20 mg 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 continued for a further 6 weeks.

Elderly

The dosage regimen recommended for elderly patients 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 20 mg tablets should be administered at the end of dialysis or thereafter since some of the active ingredient is removed via dialysis.

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).

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to other H2-receptor antagonists.

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.

4.4. Special warnings and precautions for use

Gastric neoplasm

The presence of gastric malignancy should be excluded prior to the use of famotidine for the treatment of gastric ulcers. Symptomatic response of gastric ulcer following treatment with famotidine do not preclude the presence of gastric malignancy.

Renal dysfunction

As famotidine is excreted primarily via the kidney, caution should be exercised when treating patients who are suffering from impaired renal function. A reduction in daily dosage to 20 mg should be considered if creatinine clearance falls below 10ml/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.

4.5. Interaction with other medicinal products and other forms of interaction

No clinically important drug interactions have been identified.

Co-administration of posaconazole oral-suspension with famotidine should be avoided if possible, since famotidine may reduce the absorption of posaconazole oral-suspension during concomitant use.

Co-administration of famotidine with the tyrosine kinase inhibitors (TKIs) dasatinib, erlotinib, gefitinib, pazopanib may decrease plasma concentrations of TKIs resulting in lower efficacy, therefore co-administration of famotidine with these TKIs is not recommended. For further specific recommendations please refer to the product information of individual TKI medicinal products.

Famotidine does not interact with the cytochrome P450 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 an decrease in the absorption of atazanavir.The absorption of ketoconazole and itraconazole could be reduced. Ketoconazole should be administered two hours before administering famotidine.

Probenecid 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 may reduce the famotidine absorption and lead to lower plasma levels of famotidine. Therefore, famotidine should be administered 1-2 hours before taking an antacid.

The concomitant use of sucralfate inhibits the absorption of famotidine. Therefore, sucralfate as a rule should not be administered within two hours of the famotidine dose.

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

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.

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 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 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), including isolated cases and not known (cannot be estimated from the available data).

System Organ Class

Common

Uncommon

Rare

Very rare

Blood and lymphatic system disorders

leukopenia, thrombocytopenia, neutropenia, agranulocytosis, pancytopenia

Immune system disorders

hypersensitivity reactions (anaphylaxis, angioneurotic oedema, bronchospasm)

Metabolism and nutrition disorders

anorexia

Psychiatric disorders

reversible psychological disturbances including depression, anxiety disorders, agitation, disorientation, confusion, hallucinations, insomnia, reduced libido

Nervous system disorders

headache, dizziness

Taste disorder

convulsions, grand mal seizures (particularly in patients with impaired renal function), paresthesia, somnolence

Cardiac disorders

Atrioventricular block with H2-receptor antagonists administered intravenously, arrhythmias, QT prolongation (especially in patients with impaired renal function)

Respiratory, thoracic and mediastinal disorders

interstitial pneumonia sometimes fatal

Gastrointestinal disorders

constipation, diarrhoea

dry mouth, nausea and/or vomiting, abdominal discomfort or distension, flatulence,

Hepatobiliary disorders

liver enzyme abnormalities, hepatitis, cholestatic jaundice. Isolated cases of worsening of existing hepatic disease.

Skin and subcutaneous tissue disorders

rash, pruritus, urticaria

alopecia, Stevens Johnson syndrome/toxic epidermal necrolysis sometimes fatal

Musculoskeletal and connective tissue disorders

Arthralgia, muscle cramps

Reproductive system and breast disorders

Impotence.

General disorders and administration site conditions

fatigue

chest tightness

Investigations

increase in laboratory values (transaminases, gamma-GT, alkaline phosphatase, bilirubin)

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.

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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

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/day for more than a year without development of significant side effects.

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