Famotidine

Drug Approvals

(British Approved Name, US Adopted Name, rINN)

Pharmacopoeias. In Chin, Europe, Japan, and US.

European Pharmacopoeia, 6th ed. (Famotidine). A white or yellowish-white, crystalline powder or crystals. It exhibits polymorphism. Very slightly soluble in water and in dehydrated alcohol freely soluble in glacial acetic acid practically insoluble in ethyl acetate. It dissolves in dilute mineral acids. Protect from light.

The United States Pharmacopeia 31, 2008 (Famotidine). A white to pale yellowish-white crystalline powder. Very slightly soluble in water practically insoluble in alcohol, in acetone, in chloroform, in ether, and in ethyl acetate freely soluble in dimethylformamide and in glacial acetic acid slightly soluble in methyl alcohol. Protect from light.

Adverse Effects

As for Cimetidine. Unlike cimetidine, famotidine is reported to have little or no anti-androgenic effect, although there are isolated reports of gynaeco-mastia and impotence.

Effects on the blood

For reports of blood dyscrasias, some serious, occurring with famotidine, see under Cimetidine.

Effects on the cardiovascular system

Famotidine 40 mg daily by mouth reduced cardiac output and stroke volume, compared with placebo, cimetidine, or ranitidine in healthy subjects. Similar effects seen in another study were delayed by pretreatment with ranitidine. However, other workers have found that oral famotidine had no effect on exercise capacity or left ventricular systolic function in healthy subjects, and that famotidine 20 mg intravenously had no effect on any of the haemodynamic parameters measured in 11 critically ill patients As with other H₂-antagonists, bradycardia and AV block has been reported with famotidine, as has a case of QT prolongation.

Effects on the endocrine system

Hyperprolactinaemia and breast engorgement occurred in a woman during the fourth month of treatment with famotidine 80 mg daily she had mistakenly been given twice the usual maximum dose. Recovery occurred when famotidine was withdrawn. Transient hyperprolactinaemia and galactorrhoea have also been reported in a woman after standard doses (40 mg daily) of famotidine. There have been a few instances of impotence.

Effects on the kidneys

For mention of acute interstitial nephritis associated with H₂-antagonists, including famotidine, see under Cimetidine.

Effects on the liver

Mixed hepatocellular jaundice and acute hepatitis have been associated with use of famotidine in the latter case hepatitis later recurred when the patient was given cimetidine.

Effects on the nervous system

Similarly to other H₂-antagonists, CNS reactions have occurred with famotidine, particularly in the elderly and those with renal failure. In one report, convulsions and mental deterioration in 2 elderly patients with renal failure were associated with grossly elevated plasma and CSF concentrations of the drug symptoms resolved within 3 days of withdrawing famotidine. In another elderly patient with renal impairment, delirium was associated with use of famotidine but did not occur with cimetidine

Effects on the skin

Toxic epidermal necrolysis or erythema multiforme have been reported after use of famotidine the second patient had a recurrence with cimetidine.

Fever

Famotidine 20 mg intravenously every 12 hours was associated with hyperpyrexia in a patient with facial and cranial trauma. Rectal temperature in the 24 hours after starting famotidine was 40.5° and remained elevated for the 5 days of famotidine treatment, despite use of antipyretics. Withdrawal of famotidine resulted in a return to normal temperature within 24 hours.

Precautions

As for Cimetidine.

Hepatic impairment

For a report of increased resistance to H₂-antagonists in patients with liver cirrhosis, see Ranitidine.

Renal impairment

In patients with renal impairment, famotidine clearance is reduced and the elimination half-life increased, resulting in increased serum-drug concentrations and in some cases clinical sequelae (see Effects on the Nervous System, above). The half-life of famotidine in healthy subjects is about 3 hours, but in patients with a creatinine clearance less than 38 mL/minute or those with end-stage renal disease it has been reported to be 19.3 hours and 27.2 hours respectively.

A 50% reduction in the dose of famotidine in patients with renal impairment has therefore been recommended. However, it may not be sufficient to adjust the dose only on the basis of creatinine clearance since famotidine is partly eliminated by tubular secretion, which may also be diminished. A chart review in patients with end-stage renal disease suggested that most patients would tolerate a dose of 20 mg daily, although a few might need further adjustment to prevent mental status changes.

Haemodialysis does not effectively remove famotidine from the systemic circulation. The proportion removed depends on the type of membrane used with a high flux polysulfone membrane about 16% is reported to be removed, but only 6% with a cuprophan membrane. Continuous ambulatory peritoneal dialysis is reported to remove about 5% of a dose. Continuous haemofiltration may remove about 16% of a dose intermittent haemofiltration is reported to remove about 4% or 8%. Dosage supplements of famotidine are not required during or after dialysis or filtration procedures.

Interactions

Unlike cimetidine famotidine does not inhibit cytochrome P450, and therefore is considered to have little effect on the metabolism of other drugs. However, like other H₂-antagonists its effects on gastric pH may affect the absorption of some other drugs.

Antacids

Giving famotidine 40 mg with a 10-mL dose of antacid containing 800 mg aluminium hydroxide with 800 mg magnesium hydroxide, resulted in a decrease in the bioavailability of famotidine that was considered clinically insignificant. Giving famotidine with a 30-mL dose of the same antacid resulted in a greater reduction in the absorption of famotidine from the gastrointestinal tract, but the interaction could be minimised by separating ingestionby 2 hours.

Probenecid

Probenecid in a total dose of 1500 mg had a significant effect on the pharmacokinetics of famotidine 20 mg in 8 healthy subjects. The maximum serum concentration of famotidine and the area under the concentration/time curve were significantly increased and renal clearance significantly reduced.

These effects were explained by inhibition of the renal tubular secretion of famotidine by probenecid.

Theophylline

Although famotidine is considered not to interfere with the metabolism of other drugs there is a report of a clinically significant interaction with theophylline.

Pharmacokinetics

Famotidine is readily but incompletely absorbed from the gastrointestinal tract with peak concentrations in plasma occurring 1 to 3 hours after oral doses. The bio-availability of oral famotidine is about 40 to 45% and is not significantly affected by the presence of food. The elimination half-life from plasma is reported to be about 3 hours and is prolonged in renal impairment. Famotidine is weakly bound, about 15 to 20%, to plasma proteins. A small proportion of famotidine is metabolised in the liver to famotidine S-oxide. About 25 to 30% of an oral dose, and 65 to 70% of an intravenous dose, is excreted unchanged in the urine in 24 hours, primarily by active tubular secretion. Famotidine is also found in breast milk.

Children

Famotidine 300 micrograms/kg intravenously was given to 10 children aged 2 to 7 years, after cardiac surgery and before extubation, to prevent aspiration. This dose (equivalent to about 20 mg in adults) induced a rise in the intragastric pH within 1 hour of being given and the pH remained above 3.5 for about 9 hours. The mean elimination half-life was 3.3 hours, similar to the value in healthy adults and it was considered that doses in children need therefore only be adjusted according to body-weight and renal function.

This conclusion was supported by a review of 8 studies in children over 1 year of age. Conversely, in infants aged 5 to 19 days, the mean elimination half-life was prolonged (10.5 hours) secondary to reduced renal clearance. This was confirmed by another study, which indicated that reduced clearance was found in infants under 3 months of age, but that pharmacokinetics in older infants were similar to those previously reported for children and adults.

Distribution into breast milk

The peak concentration of famotidine in breast milk, which occurred in 8 women 6 hours after an oral dose of 40 mg, was similar to the peak plasma concentration which occurred 2 hours after the dose.

Enterohepatic recirculation

Some individuals have a second peak in the plasma concentration of famotidine, which could be due to enterohepatic recirculation. However, a maximum of 0.43% of a dose of famotidine was excreted in the bile of 2 patients following single doses of 20 mg intravenously or 40 mg by mouth indicating that significant recirculation had not occurred.

Uses and Administration

Famotidine is a histamine H₂-antagonist with actions and uses similar to those of cimetidine. Famotidine may be given orally or intravenously. In the management of benign gastric and duodenal ulceration the dose is 40 mg daily orally at bedtime, for 4 to 8 weeks. A dose of 20 mg twice daily has also been given. A maintenance dose of 20 mg at bedtime may be given to prevent recurrence of duodenal ulceration.

In gastro-oesophageal reflux disease the recommended oral dose is 20 mg twice daily for 6 to 12 weeks, or up to 40 mg twice daily if there is oesophageal ulceration. A maintenance dose of 20 mg twice daily may be given to prevent recurrence. For the short-term symptomatic relief of heartburn or non-ulcer dyspepsia a dose of 10 mg up to twice daily is suggested. In the Zollinger-Ellison syndrome the initial oral dose is 20 mg every 6 hours, increased as necessary doses up to 800 mg daily have been used.

The usual dose of famotidine by the intravenous route is 20 mg and may be given by injection over at least 2 minutes or as an infusion over 15 to 30 minutes the dose may be repeated every 12 hours. Doses of famotidine should be reduced in patients with renal impairment (see below).

Administration

Although famotidine is most usually given as a film-coated tablet, an alternative wafer formulation, designed to dissolve on the tongue without the need for water, has also been developed.

Parenteral formulations of famotidine are also available in some countries. Although licensed product information recommends that intravenous injections be given over at least 2 minutes, a study that compared rapid intravenous injection (over up to 1 minute) with slow intravenous infusion found both to be safe. Continuous infusion has however been reported by others to be more effective in the prevention of stress ulceration than bolus injection.

Administration in renal impairment

The dosage of famotidine should be reduced in patients with renal impairment. In the UK, a 50% reduction is suggested for patients whose creatinine clearance is less than 10 mL/minute in the USA this reduction is recommended in all those with creatinine clearance less than 50 mL/minute. Alternatively, the dosage interval may be prolonged to 36 to 48 hours.

Immunomodulation

MALIGNANT NEOPLASMS.

References to the use of adjuvant famotidine in patients with malignant neoplasms, including use with interleukin-2 infusions.

Schizophrenia

There are reports of improvement in schizophrenic symptoms in patients given famotidine.

Preparations

British Pharmacopoeia 2008: Famotidine Tablets

The United States Pharmacopeia 31, 2008: Famotidine for Oral Suspension Famotidine Injection Famotidine Tablets

Proprietary Preparations

Argentina: Ulcelac

Australia:: Amfamox Ausfam Famohexal Pamacid Pepcid Pepcidine Pepzan

Austria: Eradix Famohexal Famosin Pepcid Sodexx Famotidine Tetacid Ulcusan

Belgium: Pepcidine

Brazil: Famodine Famoset Famotid Famotil Famox Famoxil

Canada: Acid Control Acid Halt Maalox H Acid Controller Pepcid Peptic Guard Ulcidine

Chile: Anul-bet Fibonel Gastrium

Czech Republic: Famosan Quamatel Ulceran Ulfamid

Denmark: Pepcidin

Finland: Pepcid Pepcidin

France: Pepcidac Pepcline

Germany: Fadul Famo Famobeta Famonerton Pepcid Pepdul

Greece: Ansilan Banatin Cepal Esseldon Gasterogen Imposergon Mostrelan Panalba Peptan Rosagenus Sedanium-R Vexurat

Hong Kong: Ausfam Beilande Fadine Famine Famocid Famodine Famolta Famopsin Famotin Famox Gastrodomina LAfamo Marmodine Motidine Pepcidine Phyzidine Quamatel Servipep Ulceran Vida Famodine

Hungary: Motidin Peptigal Quamatel Servipep

India: Blocacid Fadine Famodin Famonite Famowal Famtac Fudone Ulcimax

Indonesia: Antidine Corocyd Denufam Faberdin Facid Famocid Fluktan Gasfamin Gaster Gestofam Ifamul Interfam Lexmodine Nulcefam Pompaton Promocid Purifam Regastin Renapepsa Tismafam Ulcerid Ulfam Ulmo

Ireland: Pepcid

Israel: Apogastine Famo Gastro Rogasti Zarex

Italy: Famodil Gastridin Motiax

Japan: Gaster

Malaysia: Acidine Fadinef Famopsin Pepcidine Pepzan Ulceran Voker

Mexico: Adiatin Amofat Androtin Durater Eufatin Fabutin Fagatrim Famoxal Fatoril Fawodin Ludex Pepcidine Sertidine Sigafam Ultidin

Norway: Famotal Pepcid Pepcidin

New Zealand: Famox Pepcid Pepcidine Pepzan

Philippines: Famorila Famtine H2 Bloc Hista-Bloc Moticl Pepcidine Ulcefam

Poland: Famidyna Famogast Quamatel Ulfamid

Portugal: Digeslit Dinul Dipsin Fatidin Gastopride Gastrifam Lasa Mensoma Nulceran Pepcidina

Singapore: Blocacid Famoc Famopril Famopsin Famotin Famox Motidine Pepcidine Pepzan Ulceran

Spain: Brolin Confobos Cronol Digervin Dispromil Eviantrina Fagastril Famokey Famulcer Fanosin Fanox Gastenin Gastrion Gastrodomina Gastropen Ingastri Invigan Nos Nulcerin Pepcid Rubacina Tairal Tamin Tipodex Ulcetrax Ulgarine Vagostal

Sweden: Pepcid Pepcidin

Switzerland: Pepcid Pepcidine

Thailand: Agufam Fadine Famoc Famocid Famonox Famopsin Famosia Famotab Famotin Fasidine Motidine Pepcidine Pepcine Pepdenal Pepfamin Peptoci Pepzan Pharmotidine Ulceran Ulcofam Ulfamet

Turkey: Duovel Famec Famo Famodin Famogast Famoser Famotep Famotsan Gasterol Gastifam Gastrofam Gastrosidin Neotab Nevofam Notidin Pepdif

United Arab Emirates: Famotec

UK: Pepcid Ultra Heartburn Relief

USA: Mylanta AR Acid Reducer Pepcid

Venezuela: Dinamot Fadipina Famogel Famulcer Isomina Klinotal Medalin Neutracid Pepcidine Ulcenol.

Multi-ingredient

Argentina: Actual Megalex Antiacido Mylanta Extra

Canada: Pepcid Complete

Finland: Pepcid Duo

France: Pepcidduo

Germany: Pepciddual

Indonesia: Neosanmag Fast Promag Double Action

Italy: Pepciddual

Mexico: Facidex Total

Norway: Pepcidduo

Spain: Pepdual

Sweden: Pepcid Duo

UK: Pepcidtwo

USA: Pepcid Complete

The symbol denotes a preparation no longer actively marketed.