FAMOTIDINE- famotidine tablet, film coated
Mylan Institutional Inc.
Famotidine is a histamine H 2 -receptor antagonist. Famotidine is N’ -(aminosulfonyl)-3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propanimidamide. The molecular formula of famotidine is C 8 H 15 N 7 O 2 S 3 and its molecular weight is 337.45. Its structural formula is:
Famotidine, USP is a white to pale yellow crystalline compound that is freely soluble in glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol.
Each tablet for oral administration contains either 20 mg or 40 mg of famotidine. Each tablet also contains the following inactive ingredients: D&C Yellow No. 10 Aluminum Lake, FD&C Yellow No. 6 Aluminum Lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, povidone, pregelatinized starch (corn), sodium lauryl sulfate, sodium starch glycolate and titanium dioxide. In addition the 20 mg tablet contains FD&C Blue No. 2 Aluminum Lake and triacetin and the 40 mg tablet contains FD&C Blue No. 1 Aluminum Lake and glyceryl triacetate.
Famotidine is a competitive inhibitor of histamine H 2 -receptors. The primary clinically important pharmacologic activity of famotidine is inhibition of gastric secretion. Both the acid concentration and volume of gastric secretion are suppressed by famotidine, while changes in pepsin secretion are proportional to volume output.
In normal volunteers and hypersecretors, famotidine inhibited basal and nocturnal gastric secretion, as well as secretion stimulated by food and pentagastrin. After oral administration, the onset of the antisecretory effect occurred within one hour; the maximum effect was dose dependent, occurring within 1 to 3 hours. Duration of inhibition of secretion by doses of 20 mg and 40 mg was 10 to 12 hours.
Single evening oral doses of 20 mg and 40 mg inhibited basal and nocturnal acid secretion in all subjects; mean nocturnal gastric acid secretion was inhibited by 86% and 94%, respectively, for a period of at least 10 hours. The same doses given in the morning suppressed food stimulated acid secretion in all subjects. The mean suppression was 76% and 84%, respectively, 3 to 5 hours after administration, and 25% and 30%, respectively, 8 to 10 hours after administration. In some subjects who received the 20 mg dose, however, the antisecretory effect was dissipated within 6 to 8 hours. There was no cumulative effect with repeated doses. The nocturnal intragastric pH was raised by evening doses of 20 mg and 40 mg of famotidine to mean values of 5 and 6.4, respectively. When famotidine was given after breakfast, the basal daytime interdigestive pH at 3 and 8 hours after 20 mg or 40 mg of famotidine was raised to about five.
Famotidine had little or no effect on fasting or postprandial serum gastrin levels. Gastric emptying and exocrine pancreatic function were not affected by famotidine.
Systemic effects of famotidine in the CNS, cardiovascular, respiratory or endocrine systems were not noted in clinical pharmacology studies. Also, no anti-androgenic effects were noted (see ADVERSE REACTIONS). Serum hormone levels, including prolactin, cortisol, thyroxine (T 4 ), and testosterone, were not altered after treatment with famotidine.
Famotidine is incompletely absorbed. The bioavailability of oral doses is 40% to 45%. Bioavailability may be slightly increased by food, or slightly decreased by antacids; however, these effects are of no clinical consequence. Famotidine undergoes minimal first-pass metabolism. After oral doses, peak plasma levels occur in 1 to 3 hours. Plasma levels after multiple doses are similar to those after single doses. Fifteen to 20% of famotidine in plasma is protein bound. Famotidine has an elimination half-life of 2.5 to 3.5 hours. Famotidine is eliminated by renal (65% to 70%) and metabolic (30% to 35%) routes. Renal clearance is 250 to 450 mL/min, indicating some tubular excretion. Twenty-five to 30% of an oral dose and 65% to 70% of an intravenous dose are recovered in the urine as unchanged compound. The only metabolite identified in man is the S-oxide.
There is a close relationship between creatinine clearance values and the elimination half-life of famotidine. In patients with severe renal insufficiency, i.e., creatinine clearance less than 10 mL/min, the elimination half-life of famotidine may exceed 20 hours and adjustment of dose or dosing intervals in moderate and severe renal insufficiency may be necessary (see PRECAUTIONS, DOSAGE AND ADMINISTRATION).
In elderly patients, there are no clinically significant age related changes in the pharmacokinetics of famotidine. However, in elderly patients with decreased renal function, the clearance of the drug may be decreased (see PRECAUTIONS: Geriatric Use).
In a U.S. multicenter, double-blind study in outpatients with endoscopically confirmed duodenal ulcer, orally administered famotidine was compared to placebo. As shown in Table 1, 70% of patients treated with famotidine 40 mg h.s. were healed by week 4.
Famotidine40 mg h.s. (N = 89)
Famotidine20 mg b.i.d. (N = 84)
Placeboh.s. (N = 97)
Patients not healed by week 4 were continued in the study. By week 8, 83% of patients treated with famotidine had healed vs. 45% of patients treated with placebo. The incidence of ulcer healing with famotidine was significantly higher than with placebo at each time point based on proportion of endoscopically confirmed healed ulcers.
In this study, time to relief of daytime and nocturnal pain was significantly shorter for patients receiving famotidine than for patients receiving placebo; patients receiving famotidine also took less antacid than the patients receiving placebo.
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