Source: Υπουργείο Υγείας (CY) Revision Year: 2018 Publisher: Remedica Ltd, Aharnon Str., Limassol Industrial Estate, 3056 Limassol, Cyprus
Pharmacotherapeutic group: Drugs for acid related disorders; Drugs for peptic ulcer and gastro-oesophageal reflux disease (GORD)
ATC Code: A02BA03
Famotidine is a competitive histamine H2-receptor antagonist which leads to an inhibition of acid secretion mediated by H2-receptors. Beside the acidity the pepsin content and the volume of basal gastric juice as well as that formed after stimulation is reduced. A pharmacological effect on the CNS, immunological, cardiovascular or respiratory parameters could not be observed.
After oral administration the effect begins within one hour and reaches its maximum after 1-3 hours.
Single oral doses of 20 and 40 mg reliably inhibited basal nocturnal acid secretion. Mean gastric acid secretion was inhibited over at least 10 hours by 86 to 94%. The same doses administered in the morning suppressed the acid secretion stimulated by food 3-5 hours after administration by, on average, 76 to 84% and 8-10 hours after ingestion by 25 to 30%. However, the duration of action of the 20 mg dose in some subjects lasted 6-8 hours. Repeated doses did not lead to an accumulation of active constituent.
The nocturnal basal intragastric pH value was elevated by evening administration of 20 and 40 mg famotidine to an average of 5 and 6.4 respectively. If famotidine was taken after breakfast the pH value after 3 and after 8 hours was increased on the 20 mg as well as the 40 mg dose of famotidine to about 5.
Fasting and postprandial serum gastrin concentrations were not influenced by famotidine or only very slightly. Emptying of the stomach and exocrine pancreatic function were not affected by famotidine. The same applies to hepatic and portal blood flow. Famotidine had no effect on endocrinological functions either. Hormone concentrations of prolactin, cortisone, thyroxine (T4) and testosterone remained unchanged on treatment with famotidine.
Famotidine kinetics is linear.
Famotidine is quickly absorbed after oral administration.
Peak plasma concentrations are achieved in approximately 1-3.5 hours after administration of famotidine. Peak plasma concentrations are approximately 0.04 – to 0.06 μg/ml, after administration of 20 mg famotidine and 0.075 to 0.1 μg/ml after administration of 40 mg famotidine. Repeated administration does not lead to an accumulation of the active ingredient. Famotidine absorption is not influenced by concomitant food intake.
To a limited extent, famotidine is found in the cerebrospinal fluid. The fluid/plasma ratio 4 hours after administering 40 mg of famotidine was a mean of 0.1.
Oral bioavailability is about 40%.
Famotidine is excreted into maternal milk. 6 hours after oral application a milk/plasma ratio of 1.78 was reached. The elimination half-life in plasma is 2.6 to 4 hours.
Up to 30-35% of the active ingredient is metabolised in the liver; a sulfoxide metabolite is formed.
24 hours after oral administration 25-30% of the active ingredient is excreted via the urine unchanged; after intravenous administration, 65-70% is excreted unchanged in urine. Renal clearance is 250-450 ml/min which indicates tubular excretion. A slight amount can be eliminated as sulfoxide.
As renal function declines, renal and total clearance of famotidine decrease without there being an increase in non-renal elimination. The elimination half-life after intravenous injection of a single dose of 20 mg or 10 mg of famotidine is increased to 4.5-9 hours in moderate renal insufficiency (creatinine clearance 60-30 ml/min), to 10-12 hours in severe renal insufficiency (creatinine clearance <30 ml/min) and to 18-27 hours in patients with terminal insufficiency or anuria.
The amount of unchanged famotidine excreted with the urine is reduced to 60% in patients with moderate renal insufficiency. In cases of severe renal insufficiency it is only 25%.
Depending on the dialysis procedure (haemofiltration, 5-hour haemodialysis or continuous haemofiltration), dialysis patients have an elimination half-life of 7-14 hours after intravenous administration of 20 mg of famotidine after oral administration of 20 mg of famotidine it is 22.5 hours.
The pharmacokinetics of famotidine are unchanged in liver function impairment.
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 dosage.
Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenicity and toxicity to reproduction.
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