Famotidine Information
Famotidine ()
Famotidine () Description
The active ingredient in Famotidine () injection, USP is a histamine H-receptor antagonist. Famotidine () is -(aminosulfonyl)-3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propanimidamide. The empirical formula of Famotidine () is CHNOS and its molecular weight is 337.43. Its structural formula is:
Famotidine () 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.
Famotidine () injection, USP is supplied as a sterile concentrated solution for intravenous injection. Each mL of the solution contains 10 mg of Famotidine () and the following inactive ingredients: L-aspartic acid 4 mg, mannitol 20 mg, and Water for Injection q.s. 1 mL. The multidose injection also contains benzyl alcohol 0.9% added as preservative.
Famotidine () Clinical Pharmacology In Adults
Famotidine () is a competitive inhibitor of histamine H-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 one to three hours. Duration of inhibition of secretion by doses of 20 and 40 mg was 10 to 12 hours.
After intravenous administration, the maximum effect was achieved within 30 minutes. Single intravenous doses of 10 and 20 mg inhibited nocturnal secretion for a period of 10 to 12 hours. The 20 mg dose was associated with the longest duration of action in most subjects.
Single evening oral doses of 20 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 and 40 mg of Famotidine () to mean values of 5.0 and 6.4, respectively. When Famotidine () was given after breakfast, the basal daytime interdigestive pH at 3 and 8 hours after 20 or 40 mg of Famotidine () was raised to about 5.
Famotidine () had little or no effect on fasting or postprandial serum gastrin levels. Gastric emptying and exocrine pancreatic function were not affected by Famotidine () .
Orally administered Famotidine () is incompletely absorbed and its bioavailability is 40 to 45%. 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 ).
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 ).
Famotidine () Pharmacokinetics
Plasma clearance is reduced and elimination half-life is prolonged in pediatric patients 0 to 3 months of age compared to older pediatric patients. The pharmacokinetic parameters for pediatric patients, ages >3 months to 15 years, are comparable to those obtained for adults.
Bioavailability studies of 8 pediatric patients (11 to 15 years of age) showed a mean oral bioavailability of 0.5 compared to adult values of 0.42 to 0.49. Oral doses of 0.5 mg/kg achieved AUCs of 645 ± 249 ng-hr/mL and 580 ± 60 ng-hr/mL in pediatric patients
Famotidine () Pharmacodynamics
Pharmacodynamics of Famotidine () were evaluated in 5 pediatric patients 2 to 13 years of age using the sigmoid E model. These data suggest that the relationship between serum concentration of Famotidine () and gastric acid suppression is similar to that observed in one study of adults ().
Five published studies () examined the effect of Famotidine () on gastric pH and duration of acid suppression in pediatric patients. While each study had a different design, acid suppression data over time are summarized as follows:
The duration of effect of Famotidine () I.V. 0.5 mg/kg on gastric pH and acid suppression was shown in one study to be longer in pediatric patients
Famotidine () Indications And Usage
Famotidine () injection, USP supplied as a concentrated solution for intravenous injection, is intended for intravenous use only. Famotidine () injection, USP is indicated in some hospitalized patients with pathological hypersecretory conditions or intractable ulcers, or as an alternative to the oral dosage forms for short term use in patients who are unable to take oral medication for the following conditions:
Famotidine () is also indicated for the short term treatment of esophagitis due to GERD including erosive or ulcerative disease diagnosed by endoscopy (see ).
Famotidine () Contraindications
Hypersensitivity to any component of these products. 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 H-receptor antagonists.
Famotidine () Precautions
In a 106 week study in rats and a 92 week study in mice given oral doses of up to 2000 mg/kg/day (approximately 2500 times the recommended human dose for active duodenal ulcer), there was no evidence of carcinogenic potential for Famotidine () .
Famotidine () was negative in the microbial mutagen test (Ames test) using and with or without rat liver enzyme activation at concentrations up to 10,000 mcg/plate. In studies in mice, with a micronucleus test and a chromosomal aberration test, no evidence of a mutagenic effect was observed.
In studies with rats given oral doses of up to 2000 mg/kg/day or intravenous doses of up to 200 mg/kg/day, fertility and reproductive performance were not affected.
Use of Famotidine () in pediatric patients
Two pharmacokinetic studies in pediatric patients 3 months to 1 year of age is similar to that seen in older pediatric patients (1 to 15 years of age) and adults. In contrast, pediatric patients 0 to 3 months of age had Famotidine () clearance values that were 2- to 4-fold less than those in older pediatric patients and adults. These studies also show that the mean bioavailability in pediatric patients
In a double-blind, randomized, treatment-withdrawal study, 35 pediatric patients
These studies suggest that a starting dose of 0.5 mg/kg/dose of Famotidine () oral suspension may be of benefit for the treatment of GERD for up to 4 weeks once daily in patients
Use of Famotidine () in pediatric patients 1 to 16 years of age is supported by evidence from adequate and well-controlled studies of Famotidine () in adults, and by the following studies in pediatric patients: In published studies in small numbers of pediatric patients 1 to 15 years of age, clearance of Famotidine () was similar to that seen in adults. In pediatric patients 11 to 15 years of age, oral doses of 0.5 mg/kg were associated with a mean area under the curve (AUC) similar to that seen in adults treated orally with 40 mg. Similarly, in pediatric patients 1 to 15 years of age, intravenous doses of 0.5 mg/kg were associated with a mean AUC similar to that seen in adults treated intravenously with 40 mg. Limited published studies also suggest that the relationship between serum concentration and acid suppression is similar in pediatric patients 1 to 15 years of age as compared with adults. These studies suggest that the starting dose for pediatric patients 1 to 16 years of age is 0.25 mg/kg intravenously (injected over a period of not less than two minutes or as a 15-minute infusion) q 12 h up to 40 mg/day.
While published uncontrolled clinical studies suggest effectiveness of Famotidine () in the treatment of peptic ulcer, data in pediatric patients are insufficient to establish percent response with dose and duration of therapy. Therefore, treatment duration (initially based on adult duration recommendations) and dose should be individualized based on clinical response and/or gastric pH determination and endoscopy. Published uncontrolled studies in pediatric patients have demonstrated gastric acid suppression with doses up to 0.5 mg/kg intravenously q 12 h.
Of the 4,966 subjects in clinical studies who were treated with Famotidine () , 488 subjects (9.8%) were 65 and older, and 88 subjects (1.7%) were greater than 75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. However, greater sensitivity of some older patients cannot be ruled out.
No dosage adjustment is required based on age (see ). This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Dosage adjustment in the case of moderate or severe renal impairment is necessary (see and ).
Famotidine () Adverse Reactions
The adverse reactions listed below have been reported during domestic and international clinical trials in approximately 2500 patients. In those controlled clinical trials in which Famotidine () tablets were compared to placebo, the incidence of adverse experiences in the group which received Famotidine () tablets, 40 mg at bedtime, was similar to that in the placebo group.
The following adverse reactions have been reported to occur in more than 1% of patients on therapy with Famotidine () in controlled clinical trials, and may be causally related to the drug: headache (4.7%), dizziness (1.3%), constipation (1.2%) and diarrhea (1.7%).
The following other adverse reactions have been reported infrequently in clinical trials or since the drug was marketed. The relationship to therapy with Famotidine () has been unclear in many cases. Within each category the adverse reactions are listed in order of decreasing severity:
The adverse reactions reported for Famotidine () tablets may also occur with Famotidine () injection, USP. In addition, transient irritation at the injection site has been observed with Famotidine () injection, USP.
Famotidine () Overdosage
The adverse reactions in overdose cases are similar to the adverse reactions encountered in normal clinical experience (see ). Oral doses of up to 640 mg/day have been given to adult patients with pathological hypersecretory conditions with no serious adverse effects. In the event of overdosage, treatment should be symptomatic and supportive. Unabsorbed material should be removed from the gastrointestinal tract, the patient should be monitored, and supportive therapy should be employed.
The intravenous LD of Famotidine () for mice and rats ranged from 254 to 563 mg/kg and the minimum lethal single I.V. dose in dogs was approximately 300 mg/kg. Signs of acute intoxication in I.V. treated dogs were emesis, restlessness, pallor of mucous membranes or redness of mouth and ears, hypotension, tachycardia and collapse. The oral LD of Famotidine () in male and female rats and mice was greater than 3000 mg/kg and the minimum lethal acute oral dose in dogs exceeded 2000 mg/kg. Famotidine () did not produce overt effects at high oral doses in mice, rats, cats, and dogs, but induced significant anorexia and growth depression in rabbits starting with 200 mg/kg/day orally.
Famotidine () Dosage And Administration
In some hospitalized patients with pathological hypersecretory conditions or intractable ulcers, or in patients who are unable to take oral medication, Famotidine () injection, USP may be administered until oral therapy can be instituted.
The recommended dosage for Famotidine () injection, USP in adult patients is 20 mg intravenously q 12 h.
The doses and regimen for parenteral administration in patients with GERD have not been established.
Famotidine () How Supplied
FOR INTRAVENOUS USE ONLY
Famotidine () injection, USP 10 mg per 1 mL, is a non-preserved, clear, colorless solution and is supplied as follows:
Famotidine () injection, USP 10 mg per 1 mL, is a clear, colorless solution and is supplied as follows:
Famotidine ()
Famotidine () Principal Display Panel - Mg/ Ml Vial Carton
NDC 0069-0121-02 Contains 25 of NDC 0069-0121-01
For Intravenous Use Only After Dilution.
Famotidine () Principal Display Panel - Mg/ Ml Vial Carton
NDC 0069-0125-02 Contains 10 of NDC 0069-0125-01
For Intravenous Use Only After Dilution.
Famotidine () Principal Display Panel - Mg/ Ml Vial Carton
NDC 0069-0126-02 Contains 10 of NDC 0069-0126-01
For Intravenous Use Only After Dilution.
