Famotidine

INDICATIONS AND USAGE Famotidine Injection is supplied as a premixed solution in GALAXY plastic containers and is intended for intravenous use only. Famotidine Injection 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: 1. Short term treatment of active duodenal ulcer. Most adult patients heal within 4 weeks; there is rarely reason to use famotidine at full dosage for longer than 6 to 8 weeks. Studies have not assessed the safety of famotidine in uncomplicated active duodenal ulcer for periods of more than eight weeks. 2. Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of an active ulcer. Controlled studies in adults have not extended beyond one year. 3. Short term treatment of active benign gastric ulcer. Most adult patients heal within 6 weeks. Studies have not assessed the safety or efficacy of famotidine in uncomplicated active benign gastric ulcer for periods of more than 8 weeks. 4. Short term treatment of gastroesophageal reflux disease (GERD). Famotidine is indicated for short term treatment of patients with symptoms of GERD (see CLINICAL PHARMACOLOGY IN ADULTS, Clinical Studies ). Famotidine is also indicated for the short term treatment of esophagitis due to GERD including erosive or ulcerative disease diagnosed by endoscopy (see CLINICAL PHARMACOLOGY IN ADULTS, Clinical Studies ). 5. Treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison Syndrome, multiple endocrine adenomas) (see CLINICAL PHARMACOLOGY IN ADULTS, Clinical Studies ).

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 may be administered until oral therapy can be instituted. The recommended dosage for Famotidine Injection 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. Dosage for Pediatric Patients <1 year of age Gastroesophageal Reflux Disease (GERD) See PRECAUTIONS, Pediatric Patients <1 year of age . The use of intravenous famotidine in pediatric patients <1 year of age with GERD has not been adequately studied. Dosage for Pediatric Patients 1–16 years of age See PRECAUTIONS, Pediatric Patients 1-16 years of age . The studies described in PRECAUTIONS, Pediatric Patients 1–16 years of age suggest that the starting dose in pediatric patients 1-16 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 1-16 years of age have demonstrated gastric acid suppression with doses up to 0.5 mg/kg intravenously q 12 h. Dosage Adjustments for Patients with Moderate or Severe Renal Insufficiency In adult patients with moderate (creatinine clearance <50 mL/min) or severe (creatinine clearance <10 mL/min) renal insufficiency, the elimination half-life of famotidine is increased. For patients with severe renal insufficiency, it may exceed 20 hours, reaching approximately 24 hours in anuric patients. Since CNS adverse effects have been reported in patients with moderate and severe renal insufficiency, to avoid excess accumulation of the drug in patients with moderate or severe renal insufficiency, the dose of Famotidine Injection may be reduced to half the dose, or the dosing interval may be prolonged to 36-48 hours as indicated by the patient’s clinical response. Based on the comparison of pharmacokinetic parameters for famotidine in adults and pediatric patients, dosage adjustment in pediatric patients with moderate or severe renal insufficiency should be considered. Pathological Hypersecretory Conditions (e.g., Zollinger-Ellison Syndrome, Multiple Endocrine Adenomas) The dosage of famotidine in patients with pathological hypersecretory conditions varies with the individual patient. The recommended adult intravenous dose is 20 mg q 12 h. Doses should be adjusted to individual patient needs and should continue as long as clinically indicated. In some patients, a higher starting dose may be required. Oral doses up to 160 mg q 6 h have been administered to some adult patients with severe Zollinger-Ellison Syndrome. Famotidine Injection Famotidine Injection, supplied in GALAXY containers, is a 50 mL iso-osmotic solution premixed with 0.9% sodium chloride for administration as an infusion over a 15-30 minute period. This premixed solution is for intravenous use only using sterile equipment.

CONTRAINDICATIONS Hypersensitivity to any component of this product. Cross sensitivity in this class of compounds has been observed. Therefore, Famotidine Injection should not be administered to patients with a history of hypersensitivity to other H 2 -receptor antagonists.

Drug Interactions Drugs Dependent on Gastric pH for Absorption Famotidine can reduce the absorption of other drugs, due to its effect on reducing intragastric acidity, leading to loss of efficacy of the concomitant drug. See the prescribing information for other drugs dependent on gastric pH for absorption. Tizanidine (CYP1A2 Substrate) Although not studied clinically, famotidine is considered a weak CYP1A2 inhibitor. Concomitant use of tizanidine, a CYP1A2 substrate, with famotidine may lead to increased exposure of tizanidine and adverse reactions of hypotension, bradycardia or excessive drowsiness. Avoid concomitant use with famotidine. If use is clinically necessary, refer to the full prescribing information for tizanidine for dosage information.

Pregnancy Reproductive studies have been performed in rats and rabbits at oral doses of up to 2000 and 500 mg/kg/day, respectively, and in both species at I.V. doses of up to 200 mg/kg/day, and have revealed no significant evidence of impaired fertility or harm to the fetus due to famotidine. While no direct fetotoxic effects have been observed, sporadic abortions occurring only in mothers displaying marked decreased food intake were seen in some rabbits at oral doses of 200 mg/kg/day (250 times the usual human dose) or higher. There are, however, no adequate or well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers Studies performed in lactating rats have shown that famotidine is secreted into breast milk. Transient growth depression was observed in young rats suckling from mothers treated with maternotoxic doses of at least 600 times the usual human dose. Famotidine is detectable in human milk. Because of the potential for serious adverse reactions in nursing infants from famotidine, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

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: Body as a Whole : fever, asthenia, fatigue Cardiovascular : arrhythmia, AV block, palpitation, prolong QT interval. Gastrointestinal : cholestatic jaundice, hepatitis, liver enzyme abnormalities, vomiting, nausea, abdominal discomfort, anorexia, dry mouth Hematologic : rare cases of agranulocytosis, pancytopenia, leukopenia, thrombocytopenia Hypersensitivity : anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, conjunctival injection Musculoskeletal : musculoskeletal pain including muscle cramps, arthralgia Nervous System/Psychiatric : grand mal seizure; psychic disturbances, which were reversible in cases for which follow-up was obtained, including hallucinations, confusion, agitation, depression, anxiety, decreased libido; paresthesia; insomnia; somnolence. Convulsions, in patients with impaired renal function, have been reported. Respiratory : bronchospasm, interstitial pneumonia Skin : toxic epidermal necrolysis/Stevens Johnson syndrome, alopecia, acne, pruritus, dry skin, flushing Special Senses : tinnitus, taste disorder Other : rare cases of impotence and rare cases of gynecomastia have been reported; however, in controlled clinical trials, the incidences were not greater than those seen with placebo. The adverse reactions reported for famotidine tablets may also occur with famotidine for oral suspension, famotidine injection in Galaxy plastic container, and famotidine injection. In addition, transient irritation at the injection site has been observed with famotidine injection. Pediatric Patients In a clinical study in 35 pediatric patients <1 year of age with GERD symptoms [e.g., vomiting (spitting up), irritability (fussing)], agitation was observed in 5 patients on famotidine that resolved when the medication was discontinued.