Archived – Important Safety Information Famotidine

Important Safety Information Famotidine

Clinically important safety labelling change for Prescription Strength of Famotidine: dosage adjustments for patients with moderate and severe renal impairment

July 10, 2001

Dear Health Professional(s),

The purpose of this communication is to inform you of clinically important safety information for famotidine, concerning the need for dosage adjustments for patients with moderate (creatinine clearance 30-50 ml/minute) and severe (creatinine clearance less than 30 ml/minute) renal insufficiency. Since elderly patients are more likely to have a decreased renal function, care should be taken in dose selection. Recently, the MedWatch office of the U.S. FDA posted an Important Medical Safety Alert with a Summary of Pepcid (famotidine) labelling changes. Similar precautions apply to all prescription strengths of Famotidine.

Famotidine is known to be substantially excreted by the kidney. There is a close relationship between creatinine clearance values and the elimination half-life of famotidine. To avoid excess accumulation of famotidine in patients with moderate or severe renal insufficiency, the dose of famotidine should be reduced by half-the dose or the dosing interval may be prolonged to 36-48 hours as indicated by the patient's clinical response.

The following revisions to the Product Monograph are being considered:

• Precautions - Patients with Moderate or Severe Renal Insufficiency Since CNS adverse effects (confusion, disorientation, nightmares, hallucination, convulsion) have been reported in patients with moderate and severe renal insufficiency, longer intervals between doses or lower doses may need to be used in patients with moderate (creatinine clearance 30 - 50 ml/min) or severe (creatinine clearance less than 30 ml/min) to adjust for the longer elimination half-life of famotidine.
• Precautions - Use in Elderly Patients No dose adjustment is required based on age. 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.
• Dosage and Administration - Dosage Adjustment for Patients with Moderate or Severe Renal Insufficiency. In patients with moderate (creatinine clearance 30 - 50 ml/min) or severe (creatinine clearance less than 30 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 reactions have been reported in patients with moderate and severe renal insufficiency, to avoid excess accumulation of the drug in patients with moderate and severe renal insufficiency, the dose of famotidine should 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.

Please regularly consult the official Product Monograph for complete prescribing information or contact the manufacturer for additional information.

Famotidine is marketed in Canada under the following brand names:

original signed by

Barbara Rotter, Ph.D.
Gastroenterology, Oncology and Hematology Unit
Bureau of Pharmaceutical Assessment
Tel: (613) 941-0394, Fax: (613) 941-1365

References:

1. Rodgers et al, "Famotidine associated mental status changes" Pharmacology 18:404-407, 1998.
2. Schentag et al, "Age, disease, and cimetidine disposition in healthy subjects and chronically ill patients" Clin. Pharmacol. Ther. 29:737-743, 1981.
3. Yoshimoto, K., Shigeki, S., Echizen, N., Kondo, T., Yagishita, Y., Ishizaki, T., "Famotidine-associated central nervous system reactions and plasma and cerebrospinal drug concentrations in neurospinal patients with renal failure", Clin.Pharm.Ther. 66:693-700, 1994.
4. Cantu et al., "Central nervous system reactions to histamine-2 receptor blockers", (Review Article) American College of Physicians. 144:1027-1034,1991.
5. Ostro, M.J. "Pharmacodynamics and pharmacokinetics of parenteral histamine (H2)-receptor antagonists" Amer.J.Med. 83:15-22, 1987.
6. Takabatake et al., "Pharmacokinetics of famotidine, a new H2-receptor to renal function" Eur.J.Clin.Pharmacol. 28:327- 331, 1985.
7. Odeh, M., Oliven, M. "Central nervous system reactions associated with famotidine, report of five cases", J.Clin.Gastroenterol. 27:253-254, 1998.
8. Vinayek, R., Howeard, J., Maton, P., Wank, S., Slaff, J., Gardner, J., Jensen, R. "Famotidine in the therapy of gastric hypersecretory states", Am.J.Med. 81(suppl.4b):49-59, 1986.

Any suspected adverse drug reactions can also be reported to:

Canadian Adverse Drug Reaction Monitoring Program (CADRMP)
Bureau of Licensed Product Assessment Therapeutic Products Directorate
Health Canada
Address Locator: 0201C2
Ottawa, Ontario, K1A 1B9
Tel: (613) 957-0337 or Fax: (613) 957-0335
cadrmp@hc-sc.gc.ca

The ADR Reporting Form can be found in The Canadian Compendium of Pharmaceuticals and Specialties, or on the TPD website, along with the ADR Guidelines.