Famotidine Injection

Before receiving famotidine injection,

• tell your doctor and pharmacist if you are allergic to famotidine, cimetidine, nizatidine (Axid), ranitidine (Zantac), any other medications, or any of the ingredients in famotidine injection. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have or have ever had kidney disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while receiving famotidine injection, call your doctor.

Before using famotidine, tell your doctor or pharmacist if you are allergic to it; or to other acid reducers (e.g., cimetidine, ranitidine); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: immune system problems, kidney problems, liver problems, lung problems (e.g., asthma, chronic obstructive pulmonary disease-COPD), other stomach problems (e.g., tumors).Some symptoms may actually be signs of a more serious condition. Get medical help right away if you have: heartburn with lightheadedness/sweating/dizziness, chest/jaw/arm/shoulder pain (especially with shortness of breath, unusual sweating), unexplained weight loss.This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.Older adults may be more sensitive to the side effects of this drug, especially confusion.Famotidine should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.This drug passes into breast milk. Consult your doctor before breast-feeding.

For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor or pharmacist immediately to establish a new dosing schedule. Do not double the dose to catch up.

No information provided.

There is no experience to date with deliberate overdosage. 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 LD50 of famotidine for mice and rats ranged from 254 to 563 mg/kg and the minimum lethal single IV dose in dogs was approximately 300 mg/kg. Signs of acute intoxication in IV treated dogs were emesis, restlessness, pallor of mucous membranes or redness of mouth and ears, hypotension, tachycardia and collapse. The oral LD50 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.

The active ingredient in Famotidine Injection is a histamine H2–receptor antagonist.  [1-Amino-3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]-methyl]thio]propylidene] sulfamide.  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 only.  Each mL of the solution contains 10 mg of famotidine and the following inactive ingredients: L-aspartic acid 4 mg, mannitol 20 mg, Water for Injection q.s. 1 mL and benzyl alcohol 0.9% added as preservative.

Famotidine Injection, supplied as a concentrated solution for intravenous injection, 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 8 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 (seeCLINICAL 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).

Hypersensitivity to any component of this product.  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 H2 –receptor antagonists.

There is no experience to date with deliberate overdosage.  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 LD50 of famotidine for mice and rats ranged from 254 to 563 mg/kg and the minimum lethal single IV dose in dogs was approximately 300 mg/kg.  Signs of acute intoxication in IV treated dogs were emesis, restlessness, pallor of mucous membranes or redness of mouth and ears, hypotension, tachycardia and collapse.  The oral LD50 of famotidine in male and female rats and mice was greater than 3,000 mg/kg and the minimum lethal acute oral dose in dogs exceeded 2,000 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.

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

See PRECAUTIONS ,Pediatric Use.

The studies described in PRECAUTIONS ,Pediatric Use suggest that the starting dose in 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.

No pharmacokinetic or pharmacodynamic data are available on pediatric patients under 1 year of age.

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 to 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.

Preparation of Intravenous Solutions

To prepare famotidine intravenous solutions, aseptically dilute 2 mL of Famotidine Injection (solution containing 10 mg/mL) with 0.9% Sodium Chloride Injection or other compatible intravenous solution (see Stability), to a total volume of either 5 mL or 10 mL and inject over a period of not less than 2 minutes.

To prepare famotidine intravenous infusion solutions, aseptically dilute 2 mL of Famotidine Injection with 100 mL of 5% dextrose or other compatible solution (see Stability), and infuse over a 15 to 30 minute period.

Concomitant Use of Antacids

Antacids may be given concomitantly if needed.

Stability

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

When added to or diluted with most commonly used intravenous solutions, e.g., Water for Injection, 0.9% Sodium Chloride Injection, 5% and 10% Dextrose Injection, or Lactated Ringer’s Injection, diluted Famotidine Injection is physically and chemically stable (i.e., maintains at least 90% of initial potency) for 7 days at room temperature – seeHOW SUPPLIED ,Storage.

When added to or diluted with Sodium Bicarbonate Injection, 5%, Famotidine Injection at a concentration of 0.2 mg/mL (the recommended concentration of famotidine intravenous infusion solutions) is physically and chemically stable (i.e., maintains at least 90% of initial potency) for 7 days at room temperature – see HOW SUPPLIED ,Storage.  However, a precipitate may form at higher concentrations of Famotidine Injection (>0.2 mg/mL) in Sodium Bicarbonate Injection, 5%.