Famotidine-Associated Mental Confusion in Elderly Patients

Henann, Neil E.; Carpenter, Deborah U.; Janda, Sue M.

doi:10.1177/106002808802201209

Cited by 36 publications

(8 citation statements)

References 12 publications

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“…Failure to reduce doses of famotidine in patients with severe renal impairment is known to be associated with mental status changes including confusion, agitation, delirium, irritability, and hallucinations. 27,28 Our results are consistent with several retrospective studies in more than 20,000 patients with CKD reporting that use of the MDRD equation overestimates Cl cr , leading to significantly higher drug doses compared with doses calculated by using CG. [29][30][31][32] Our median discordance of 28% for the MDRD equation is consistent with data reported in one study.…”

Section: Discussionsupporting

confidence: 89%

“…For example, use of the MDRD equation resulted in a 41% discordance rate for famotidine, in which all discordant cases would have resulted in higher doses being given to patients if the MDRD equation was used instead of the CG equation. Failure to reduce doses of famotidine in patients with severe renal impairment is known to be associated with mental status changes including confusion, agitation, delirium, irritability, and hallucinations …”

Section: Discussionmentioning

confidence: 99%

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Glomerular Filtration Rate Equations Overestimate Creatinine Clearance in Older Individuals Enrolled in the Baltimore Longitudinal Study on Aging: Impact on Renal Drug Dosing

et al. 2013

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Objectives To evaluate performance of kidney function estimation equations and to determine the frequency of drug dose discordance in an older population. Design Cross-sectional analysis of data from community-dwelling volunteers randomly selected from the Baltimore Longitudinal Study of Aging from January 1, 2005–December 31, 2010. Subjects Two hundred sixty-nine men and women with a mean ± SD age of 81 ± 6 years, mean serum creatinine concentration (Scr) of 1.1 ± 0.4 mg/dl, and mean measured 24-hour creatinine clearance (mClcr) of 53 ± 13 ml/minute. Measurements and Main Results Kidney function was estimated by using the following equations: Cockcroft-Gault (CG), Modification of Diet in Renal Disease Study (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The performance of each equation was assessed by measuring bias and precision relative to mClcr. Dose calculation errors (discordance) were determined for 10 drugs requiring renal dosage adjustments to avoid toxicity when compared to the FDA-approved dosages. The CG equation was the least biased estimate of mClcr. The MDRD and CKD-EPI equations were significantly positively biased compared to CG (mean ± SD 34 ± 20% and 22 ± 15%, respectively, p<0.001) and mClcr (29 ± 47% and 18 ± 40%, respectively, p<0.001). Rounding low Scr values (< 1.0 mg/dl) up to an arbitrary value of 1.0 mg/dL resulted in CG values (44±10 mL/min) that were significantly lower than mClcr (56±12 mL/min, p<0.001) and CG (56±15 mL/min, p<0.001). The MDRD and CKD-EPI equations had median dose discordance rates of 28.6% and 22.9%, respectively. Conclusion The MDRD and CKD-EPI equations significantly overestimated creatinine clearance (mClcr and CG) in elderly individuals. This leads to dose calculation errors for many drugs, particularly in individuals with severe renal impairment. Thus, GFR-estimating equations should not be substituted in place of the CG equation in older adults for the purpose of renal dosage adjustments. In addition, the common practice of rounding or replacing low Scr values with an arbitrary value of 1.0 mg/dL for use in the CG equation should be avoided. Additional studies that evaluate alternative eGFR equations in the older populations that incorporate pharmacokinetic and pharmacodynamic outcomes measures are needed.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Glomerular Filtration Rate Equations Overestimate Creatinine Clearance in Older Individuals Enrolled in the Baltimore Longitudinal Study on Aging: Impact on Renal Drug Dosing

et al. 2013

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“…Also ranitidine [13] and famotidine [21] have been reported to induce delirium, however, less often than is the case with cimetidine. Proton pump blockers have, in contrast to H2 blockers, only a very slightly increased risk of delirium [22].…”

Section: Histamine H2 Receptor Blockersmentioning

confidence: 99%

Drugs That Induce Delirium

Karlsson

1999

Dement Geriatr Cogn Disord

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Drug-induced delirium is often seen in clinical practice. Most knowledge about delirium-inducing drugs comes from reports on side effects, and few systematic studies have been done in the field. Delirium is strongly associated with anticholinergic activity; drugs of different classes, including tricyclic antidepressants and traditional high-dose neuroleptics, constitute a high-risk group. A large number of drugs, including benzodiazepines, sedatives, dopamine-activating drugs, antiepileptics, histamine H2 receptor blockers, digitalis and analgesics, are less frequently associated with delirious reactions and constitute a medium-high-risk group. Some of these drugs do not have anticholinergic effects but in vitro have shown to bind to muscarine receptors. The risk of inducing delirium in frail elderly and demented persons clearly suggests that drugs which might induced delirium should be avoided.

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“…CNS disturbances have now been reported with all available H2-receptor antagonists, including famotidine (Henann et al 1988). The incidence of such reactions was seemingly quite similar for each treatment, with a reported incidence ranging from 0.2 to 1.9% for ranitidine (Eandi et al 1990;Inman 1983).…”

Section: Neuropsychiatric Complicationsmentioning

confidence: 96%

Side Effects of Ranitidine

et al. 1991

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Ranitidine was first marketed in 1981; since then many patients have been treated such that much experience has been accumulated on the safety of this histamine H2-receptor antagonist in the treatment of gastroduodenal disease. A wide array of ranitidine-associated side effects has been described, but infrequently. As so much information is now available, the aim of this review is to assess the weight of evidence for a causal link between ranitidine and the reported side effects. Overall, ranitidine is well tolerated. The incidence of general side effects at less than 2% is very similar to placebo. Headaches, tiredness, dizziness and mild gastrointestinal disturbance (e.g. diarrhoea, constipation and nausea) are among the most frequent complaints, but have very seldom resulted in stopping treatment. Cardiovascular side effects are extremely rare and unpredictable with the usual doses of oral ranitidine (at most 1 in 1 million patients). They mostly comprise sinusal bradycardia and atrioventricular blockade, especially after rapid intravenous administration, receding after cessation of the drug. Clinical studies, however, have not shown a significant pharmacological effect of ranitidine on the cardiovascular system via H2-receptors, even though individual sensitivities cannot be ruled out in a few isolated reports. Ranitidine is unlikely to be directly hepatotoxic: a transient change in liver function tests has been noted in only 1 in 100 to 1 in 1000 patients. Several cases of mixed hepatitis have been reported, but very few were fully documented. The incidence of ranitidine-associated acute hepatitis has been estimated to be less than 1 in 100,000 patients. Neuropsychiatric complications may be less common and clinically quite similar to those reported with cimetidine, i.e. confusion, disorientation, hallucinations, delirium. These side effects have occurred especially in critically ill and multiple-therapy patients, or patients with chronic renal or hepatic failure, so that the direct causal link with ranitidine treatment was often difficult to ascertain. Even though an H2-receptor-mediated effect is an attractive hypothesis (since similar complications were noted with other H2-receptor antagonists), other mechanisms have been suggested to play a role, e.g. cholinergic or histaminic effects. The overall incidence of neuropsychiatric complications is probably markedly less than 1%. White cell injury (i.e. agranulocytosis) appears to be the most frequent haematological complication, even though case reports are very few and poorly documented.(ABSTRACT TRUNCATED AT 400 WORDS)

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Famotidine-Associated Mental Confusion in Elderly Patients

Cited by 36 publications

References 12 publications

Glomerular Filtration Rate Equations Overestimate Creatinine Clearance in Older Individuals Enrolled in the Baltimore Longitudinal Study on Aging: Impact on Renal Drug Dosing

Glomerular Filtration Rate Equations Overestimate Creatinine Clearance in Older Individuals Enrolled in the Baltimore Longitudinal Study on Aging: Impact on Renal Drug Dosing

Drugs That Induce Delirium

Side Effects of Ranitidine

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