FAMOTIDINE
Chemistry - An H2-receptor antagonist, famotidine occurs as a white to pale yellow, crystalline powder. It is odorless, but has a bitter taste. 740 micrograms are soluble in one ml of water.
The powder for oral suspension should be stored in tight containers at temperatures less than 40°C. After reconstitution, the resultant suspension is stable for 30 days when stored at temperatures less than 30°C.; do not freeze.
Famotidine injection should be stored in the refrigerator (2-8°C). It is compatible with most commonly used IV infusion solutions and is stable for 48 hours at room temperature when diluted in these solutions.
Although there is less veterinary experience with this agent than with either ranitidine or cimetidine, it has some potential advantages in that it suffers from fewer documented drug interaction problems and may suppress acid production longer than with either cimetidine or ranitidine. The clinical advantage of using famotidine over either drug has not been confirmed.
Distribution characteristics are not well described. In rats, the drug concentrates in the liver, pancreas, kidney and submandibular gland. Only about 15-20% is bound to plasma proteins. In rats, the drug does not cross the blood brain barrier nor the placenta. It is distributed into milk. When the drug is administered orally, about 1/3 is excreted unchanged in the urine and the remainder primarily metabolized in the liver and then excreted in the urine. After intravenous dosing, about 2/3's of a dose is excreted unchanged.
The pharmacokinetics of famotidine, ranitidine, and cimetidine have been investigated (Duran and Ravis 1993) in horses After a single IV dosage, elimination half lives of cimetidine, ranitidine and famotidine all were in the 2-3 hour range and were not significantly different. Of the three drugs tested, famotidine had a larger volume of distribution (4.28 L/kg) than either cimetidine (1.14 L/kg) or ranitidine (2.04 L/kg). Bioavailability of each of the drugs was low; famotidine (13%), ranitidine (13.5%) and cimetidine (30%).
Famotidine should be used cautiously in geriatric patients and in patients with significantly impaired hepatic or renal function. Famotidine may have negative inotropic effects and have somecardioarrhythmogenic properties. Use with caution in patients with cardiac disease.
In lab animal studies, famotidine demonstrated no detectable harm to offspring. Large doses mayaffect the mother's food intake and weight gain during pregnancy which may indirectly be harmful.
Use in pregnancy when potential benefits outweigh the risks. In rats nursing from mothersreceiving very high doses of famotidine, transient decreases in weight gain occurred.
There have been reports of famotidine causing intravascular hemolysis when given intravenouslyto cats.
Overdosage, Acute Toxicity - The minimum acute lethal dose in dogs is reported to be >2grams/kg for oral doses and approximately 300 mg/kg for intravenous doses. IV doses in dogsranging from 5-200 mg/kg IV caused vomiting, restlessness, mucous membrane pallor and rednessof the mouth and ears. Higher doses caused hypotension, tachycardia and collapse.
Because of this wide margin of safety associated with the drug, most overdoses should requireonly monitoring. In massive oral overdoses, gut emptying protocols should be considered andsupportive therapy initiated when warranted.
Unlike cimetidine or ranitidine, famotidine does not appear to inhibit hepatic cytochrome P-450 enzyme systems and dosage adjustments of other drugs (e.g., warfarin, theophylline, diazepam, procainamide, phenytoin) that are metabolized by this metabolic pathway should usually not be required.
Laboratory Considerations - Histamine2 blockers may antagonize the effects of histamine andpentagastrin in the evaluation gastric acid secretion. After using allergen extract skin tests, histamine2 antagonists may inhibit histamine responses. It is recommended that histamine2blockers be discontinued at least 24 hours before performing either of these tests.
Storage, Stability, Compatibility
Tablets should be stored in well-closed, light-resistant containers at room temperature. Tablets are assigned an expiration date of 30 months after date of manufacture.The powder for oral suspension should be stored in tight containers at temperatures less than 40°C. After reconstitution, the resultant suspension is stable for 30 days when stored at temperatures less than 30°C.; do not freeze.
Famotidine injection should be stored in the refrigerator (2-8°C). It is compatible with most commonly used IV infusion solutions and is stable for 48 hours at room temperature when diluted in these solutions.
Pharmacology - FAMOTIDINE
At the H2 receptors of the parietal cells, famotidine competitively inhibits histamine, thereby reducing gastric acid output both during basal conditions and when stimulated by food, pentagastrin, histamine or insulin. Gastric emptying time, pancreatic or biliary secretion, and lower esophageal pressures are not altered by famotidine . By decreasing the amount of gastric juice produced, H2-blockers also decrease the amount of pepsin secreted.Uses, Indications
In veterinary medicine, famotidine may be useful for the treatment and/orprophylaxis of gastric, abomasal and duodenal ulcers, uremic gastritis, stress-related or drug-in-duced erosive gastritis, esophagitis, duodenal gastric reflux and esophageal reflux.Although there is less veterinary experience with this agent than with either ranitidine or cimetidine, it has some potential advantages in that it suffers from fewer documented drug interaction problems and may suppress acid production longer than with either cimetidine or ranitidine. The clinical advantage of using famotidine over either drug has not been confirmed.
Pharmacokinetics - FAMOTIDINE
Famotidine is not completely absorbed after oral administration, but undergoes only minimal first-pass metabolism. In humans, systemic bioavailability is about 40-50%.Distribution characteristics are not well described. In rats, the drug concentrates in the liver, pancreas, kidney and submandibular gland. Only about 15-20% is bound to plasma proteins. In rats, the drug does not cross the blood brain barrier nor the placenta. It is distributed into milk. When the drug is administered orally, about 1/3 is excreted unchanged in the urine and the remainder primarily metabolized in the liver and then excreted in the urine. After intravenous dosing, about 2/3's of a dose is excreted unchanged.
The pharmacokinetics of famotidine, ranitidine, and cimetidine have been investigated (Duran and Ravis 1993) in horses After a single IV dosage, elimination half lives of cimetidine, ranitidine and famotidine all were in the 2-3 hour range and were not significantly different. Of the three drugs tested, famotidine had a larger volume of distribution (4.28 L/kg) than either cimetidine (1.14 L/kg) or ranitidine (2.04 L/kg). Bioavailability of each of the drugs was low; famotidine (13%), ranitidine (13.5%) and cimetidine (30%).
Contraindications, Precautions, Reproductive Safety
Famotidine is contraindicated in patientswith known hypersensitivity to the drug.Famotidine should be used cautiously in geriatric patients and in patients with significantly impaired hepatic or renal function. Famotidine may have negative inotropic effects and have somecardioarrhythmogenic properties. Use with caution in patients with cardiac disease.
In lab animal studies, famotidine demonstrated no detectable harm to offspring. Large doses mayaffect the mother's food intake and weight gain during pregnancy which may indirectly be harmful.
Use in pregnancy when potential benefits outweigh the risks. In rats nursing from mothersreceiving very high doses of famotidine, transient decreases in weight gain occurred.
Adverse Effects, Warnings
Because there is limited experience with this drug, its adverse effectprofile has not been determined for veterinary species. Other H2 blockers have been demonstratedto be relatively safe and exhibit minimal adverse effects. Potential adverse effects (documented inhumans) that could be seen include GI effects (anorexia, vomiting, diarrhea), headache, or drymouth or skin. Rarely, agranulocytosis may develop particularly when used concomitantly withother drugs that can cause bone marrow depression.There have been reports of famotidine causing intravascular hemolysis when given intravenouslyto cats.
Overdosage, Acute Toxicity - The minimum acute lethal dose in dogs is reported to be >2grams/kg for oral doses and approximately 300 mg/kg for intravenous doses. IV doses in dogsranging from 5-200 mg/kg IV caused vomiting, restlessness, mucous membrane pallor and rednessof the mouth and ears. Higher doses caused hypotension, tachycardia and collapse.
Because of this wide margin of safety associated with the drug, most overdoses should requireonly monitoring. In massive oral overdoses, gut emptying protocols should be considered andsupportive therapy initiated when warranted.
Drug Interactions
Stagger doses (separate by 2 hours if possible) of famotidine with antacids, metoclopramide, sucralfate, digoxin, and ketoconazole. Famotidine may exacerbate leukopenias when used with other bone marrow suppressing drugs.Unlike cimetidine or ranitidine, famotidine does not appear to inhibit hepatic cytochrome P-450 enzyme systems and dosage adjustments of other drugs (e.g., warfarin, theophylline, diazepam, procainamide, phenytoin) that are metabolized by this metabolic pathway should usually not be required.
Laboratory Considerations - Histamine2 blockers may antagonize the effects of histamine andpentagastrin in the evaluation gastric acid secretion. After using allergen extract skin tests, histamine2 antagonists may inhibit histamine responses. It is recommended that histamine2blockers be discontinued at least 24 hours before performing either of these tests.