Case Report: Oral Cimetidine Administration Causes Drug-Induced Immune Hemolytic Anemia by Eliciting the Production of Cimetidine-Dependent Antibodies and Drug-Independent Non-specific Antibodies

Previously, it was reported that multiple patients had hemolytic anemia associated with cimetidine administration, while only one patient who had received intravenous cimetidine was serologically diagnosed with drug-induced immune hemolytic anemia (DIIHA) caused by cimetidine-dependent antibodies. However, the ability of oral cimetidine intake to induce the production of antibodies has not been examined. In this study, we report a 44-year-old male patient in whom oral cimetidine administration resulted in cimetidine-dependent antibodies and drug-independent non-specific antibodies, leading to the development of DIIHA. Serological tests showed that the results of direct antiglobulin test (DAT) for anti-IgG (3+) and anti-C3d (1+) were positive. The IgM and IgG cimetidine-dependent antibodies (the highest total titer reached 4,096) were detected in the plasma incubated with O-type RBCs and 1 mg/mL cimetidine or the plasma incubated with cimetidine-coated RBCs. IgG-type drug-independent non-specific antibodies were detected in blood samples collected at days 13, 34, 41, and 82 post-drug intake. This is the first study to report that oral administration of cimetidine can elicit the production of cimetidine-dependent antibodies, leading to DIIHA, and the production of drug-independent non-specific antibodies, resulting in hemolytic anemia independent of cimetidine. Presence of pathogenic antibodies were detectable longer than 41 days. This suggests that patients with DIIHA caused by cimetidine need to be given necessary medical monitoring within 41 days after cimetidine intake.

Creatinine clearance after cimetidine administration in a new short procedure: comparison with plasma and renal clearances of iohexol

Background Creatinine clearance after cimetidine administration (Cim-CreatClr) was once proposed as a method of glomerular filtration rate (GFR) measurement, but has been largely abandoned. We investigated whether a new short procedure for Cim-CreatClr determination could be considered an appropriate method for GFR measurement. Methods A 150-min protocol involving oral cimetidine administration was developed to determine Cim-CreatClr. In total, 168 patients underwent simultaneous assessments of creatinine clearance before and after cimetidine administration [basal creatinine clearance (Basal-CreatClr) and Cim-CreatClr, respectively], renal iohexol clearance and plasma iohexol clearance (R-iohexClr and P-iohexClr, respectively). We compared the agreement between the various methods of GFR measurement, using Bland–Altman plots to determine biases, precisions (standard deviation of the biases) and accuracy (proportions of GFR values falling within 10, 15 and 30% of the mean: P10, P15 and P30, respectively). Results After cimetidine administration, Basal-CreatClr decreased by 19.8% [95% reference limits of agreement (95% LoA): −2.2 to 41.7%]. The bias between Cim-CreatClr and P-iohexClr was −0.6% (95% LoA −26.8 to 28%); the precision was 14.0%; P10, P15 and P30 were 57.1% [95% confidence interval (95% CI) 49.3 to 64.7%], 73.2% (95% CI 65.8 to 79.7%) and 97.0% (95% CI 93.2 to 99.0%), respectively. Due to the positive bias (16.7%; 95% LoA −3.6 to 36.9%) of Cim-CreatClr relative to R-iohexClr, accuracy of Cim-CreatClr relative to R-iohexClr was poor despite a good precision (10.3%). Conclusions Our study shows a high level of agreement between Cim-CreatClr and P-iohexClr. These results suggest that this short Cim-CreatClr procedure is a valid method for GFR measurement, which might be useful, in particular, in situations in which P-iohexClr is not suitable or not available.

The influence of oral cimetidine administration on creatinine clearance in chilren with chronic renal failure: A preliminary study

Background Serum creatinine and creatinine clearance are usedto assess glomerular filtration rate but have a major disadvantagesince a variable amount of creatinine is secreted in the proximaltubule. This may cause an unpredictable overestimation of GFR.Tubular creatinine secretion can be blocked by cimetidine throughcompetitive inhibition of cation transport in the proximal tubularluminal membrane.Objective Cimetidine administration might improve the reliabilityof creatinine as a marker of glomerular filtration.Methods A preliminary study with a one-group pretest-posttestdesign in 11 children with chronic renal failure. Serum cystatin Clevel as reference value was compared with creatinine clearancemeasured before and after oral ingestion of cimetidine. The doseof cimetidine was adjusted with the GFR using Schwartz formula.Statistical evaluation was done with the Wilcoxon signed rankstest.Result The mean creatinine clearance before cimetidine adminis-tration was 27.4 (SD 14.6) ml/minute/1.73 m 2 BSA, and decreasedafter cimetidine to 21.1 (SD 13,1) ml/minute/1.73 m 2 BSA (p=0.015).Conclusion Oral cimetidine was effective in inhibiting creatininetubular secretion. This study could not prove that cimetidine im-proves the accuracy of creatinine clearance

Cimetidine as a First-Line Therapy for Pedal Verruca

Can cimetidine therapy effectively stimulate the body’s immune response against warts? Several clinicians have anecdotally reported success using cimetidine against warts. Previous double-blind studies comparing cimetidine with placebo therapy have failed to statistically and scientifically corroborate those results. Between 1995 and 2002, 216 patients underwent an isolated course of oral cimetidine therapy for verruca plantaris. Our treatment outcomes closely parallel those obtained by other researchers. Cimetidine may be used as a safe, effective, lone treatment modality for verruca in all age groups. (J Am Podiatr Med Assoc 95(3): 229–234, 2005)