Pepcid (Famotidine)

What Is Pepcid (Famotidine)?

Pepcid, or Famotidine, is a medication commonly used to treat conditions related to excess stomach acid production. It belongs to a class of drugs known as H2 blockers, which work by reducing the amount of acid the stomach produces. Famotidine is often prescribed to alleviate symptoms of conditions such as gastroesophageal reflux disease (GERD), peptic ulcers, and heartburn. It can be taken orally as a tablet or liquid; its effects typically last a few hours. While generally well-tolerated, following your healthcare provider’s instructions and being aware of potential side effects or interactions with other medications is essential.

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 to plasma proteins, about 15 to 20%. A small proportion of famotidine is metabolized in the liver to famotidine S-oxide. About 25 to 30% of an oral dose and 65 to 70% of an intravenous dose are excreted unchanged in the urine in 24 hours, primarily by active tubular secretion. Famotidine is also found in breast milk.

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 managing 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 the 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, and 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 usually given as a film-coated tablet, an alternative wafer formulation designed to dissolve on the tongue without 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 at least 2 minutes, a study comparing rapid intravenous injection (over up to 1 minute) with slow intravenous infusion found both to be safe. However, others have reported continuous infusion as more effective than bolus injection in preventing stress ulceration.

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 less than 50 mL/minute of creatinine clearance. Alternatively, the dosage interval may be prolonged to 36 to 48 hours.

Immunomodulation

Malignant Neoplasms

There are reports about 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.

Over the Counter Famotidine (Pepcid)

Johnson & Johnson-Merck has won the race to bring an H(2)-receptor antagonist to the over-the-counter (OTC) market. The joint pharmaceutical venture has received marketing approval for its 10-mg preparation of famotidine (Pepcid AC Acid Controller) from the Food and Drug Administration (FDA). The product is indicated for treating and preventing heartburn and acid indigestion. Still available by prescription are 20- and 40-mg tablets of famotidine.

The manufacturer hopes to draw consumers who have been using popular antacid preparations. Product promotion, however, emphasizes that famotidine is not an antacid but works by blocking gastric acid secretion.

OTC famotidine (Pepcid) has been shown to prevent heartburn and acid indigestion when taken 1 hour before food or beverages that are expected to cause heartburn. In one efficacy study, the product prevented heartburn in 75% of cases, compared with 57% of cases with placebo. In a second study, preventive efficacy was 73% compared with 52% for placebo.

Clinical trials also assessed OTC famotidine for efficacy in relieving existing heartburn. More than 1700 men and women aged 18 to 81 were treated at 58 clinical centers in the United States. The trials encompassed more than 2300 episodes of heartburn. In one study, complete relief occurred in 70% of episodes treated with 10 mg famotidine, compared with 41% of those treated with placebo. A second study showed 67% efficacy with famotidine, compared with 53% for placebo.

The manufacturer claims significant safety advantages for OTC famotidine (Pepcid): No clinically significant interactions with other drugs have been reported, and the dose needed for efficacy is low. Furthermore, the safety profile of famotidine is well established from experience with prescription doses of the drug, which was first approved in 1986.

Pepcid AC Acid Controller is available as 10-mg tablets in 6, 12, or 18 packages. To relieve symptoms, a user should swallow one tablet with water (the tablet should not be chewed). For prevention of heartburn, one tablet should be taken 1 hour before consumption of food or drink that would be expected to produce heartburn. The maximum recommended dosage is two tablets a day.

The manufacturer is touting new easy-to-read labeling that uses icons, charts, and written information to promote understanding of the product’s use. The labeling stresses that patients should consult a physician if they have difficulty swallowing or experience persistent abdominal pain or if they have been taking the maximum daily dosage continuously for two weeks without relief.

Adverse Effects

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

Effects on the Blood

There are reports of blood dyscrasias, severe side effects associated with famotidine, see under Cimetidine.

Effects on the Cardiovascular System

Famotidine 40 mg daily taken orally reduces 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 researchers 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 hemodynamic parameters measured in 11 critically ill patients. As with other H2-antagonists, bradycardia and AV block have 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 hyperprolactinemia 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 the 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 older people 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 three days of withdrawing famotidine. In another elderly patient with renal impairment, delirium was associated with the use of famotidine but did not occur with cimetidine.

Effects on the Skin

Toxic epidermal necrolysis or erythema multiforme have been reported after the 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. The rectal temperature in the 24 hours after starting famotidine was 40.5° and remained elevated for the five days of famotidine treatment despite the 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 is 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 is 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 based on creatinine clearance only 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.

Hemodialysis does not effectively remove famotidine from the systemic circulation. The proportion removed depends on the type of membrane used. About 16% is reported to be removed with a high flux polysulfone membrane, but only 6% is removed 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 an antacid containing 800 mg aluminum 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 more significant reduction in the absorption of famotidine from the gastrointestinal tract. Still, the interaction could be minimized by separating ingestion by 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 was significantly reduced.

These effects were explained by inhibiting 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.

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) increased 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 only be adjusted according to body weight and renal function.

This conclusion was supported by a review of 8 studies in children over one year of age. Conversely, the mean elimination half-life was prolonged in infants aged 5 to 19 days (10.5 hours) secondary to reduced renal clearance. This was confirmed by another study, which indicated that reduced clearance was found in infants under three 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 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.

Drug Approvals

(British Approved Name, US Adopted Name, rINN)

Synonyms: Famotidiini; Famotidin; Famotidina; Famotidinas; Famotidinum; L-643341; MK-208; YM-11170

BAN: Famotidine

USAN: Famotidine

INN: Famotidine [rINN (en)]

INN: Famotidina [rINN (es)]

INN: Famotidine [rINN (fr)]

INN: Famotidinum [rINN (la)]

INN: Фамотидин [rINN (ru)]

Chemical name: 3-[2-(Diaminomethyleneamino)thiazol-4-ylmethylthio]-N-sulphamoylpropionamidine

Molecular formula: C8H15N7O2S3 =337.4

CAS: 76824-35-6

ATC code: A02BA03

Read code: y01QA

Pharmacopoeias. In China, Europe, Japan, and the US.

European Pharmacopoeia, 6th ed. (Famotidine). It is a white or yellowish-white crystalline powder or crystals. It exhibits polymorphism. Very slightly soluble in water and dehydrated alcohol, freely soluble in glacial acetic acid, and 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, acetone, chloroform, ether, and ethyl acetate, freely soluble in dimethylformamide and glacial acetic acid, and slightly soluble in methyl alcohol. Protect from light.

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.