Serum creatinine cimetidine

The available data on a possible interaction between histamine H2 receptor antagonists and ciclosporin are inconclusive. Whereas neither cimetidine nor ranitidine significantly altered ciclosporin pharmacokinetics, there was an increase in serum creatinine concentration in patients taking both ciclosporin and cimetidine, but not ranitidine. The clinical significance of this interaction is probably limited, and it has been attributed to competition of cimetidine with creatinine for tubular secretion (251). 

In humans, serum creatinine is dependent on non renal factors independent of kidney function e.g. muscle mass, nutritional status, infection, volume of distribution. Also, serum creatinine is dependent on renal factors that are independent of function. For example, certain drugs like trimethoprim and cimetidine elevations in serum creatinine by altering the normal elimination pathways of creatinine. In addition, in humans, alterations in serum creatinine may lag several days behind actual changes in GFR. Earher detection of AKI with a kidney specific biomarker may be essential for early and successful treatment of AKI in humans. 

Reports are inconsistent. Cimetidine and famotidine have been reported to increase cielosporin levels, whereas in other studies cimetidine, famotidine and ranitidine have been reported to not affect cielosporin levels. Both cimetidine and ranitidine have been reported to cause an increase in serum creatinine levels, in some but not all studies, but this may possibly not be a reliable indicator of increased nephrotoxicity. Isolated cases of thrombocytopenia and hepatotoxicity have been reported with ranitidine and cielosporin. 

Information about the possible interactions of ciclosporin and cimetidine, famotidine or ranitidine is inconsistent, but there appear to be very few reports of confirmed toxicity. Moreover the reported increases in serum creatinine levels seen with the H2-receptor antagonists may not be a reflection of increased nephrotoxicity (see Mechanism )- Thus there is little to suggest that concurrent use should be avoided, but good initial monitoring is advisable. 

Inhibitors of the renal cation secretion mechanism, eg, cimetidine, prolong the half-life of dofetilide. Since the QT-prolonging effects and risks of ventricular proarrhythmia are directly related to plasma concentration, dofetilide dosage must be based on the estimated creatinine clearance. Treatment with dofetilide should be initiated in hospital after baseline measurement of the rate-corrected QT interval (QTC) and serum electrolytes. A baseline QTC of > 450 ms (500 ms in the presence of an intraventricular conduction delay), bradycardia of < 50 bpm and hypokalemia are relative contraindications to its use. 

Ziemniak, J.A. Chiarmonte, D.A. Schentag, J.J. Liquid-chromatographic determination of cimetidine, its known metabolites, and creatinine in serum and urine. Clin.Chem., 1981, 27, 272-275 [serum plasma urine extracted metabolites, creatinine pharmacokinetics LOD 50 ng/mL]... 

In a small open trial 79 patients with active duodenal ulceration were treated with a 6-week course of cimetidine in doses of 1.6 g daily (13 ). No statistically significant change in the haemoglobin, white blood cell count or serum enzymes (SCOT, alkaline phosphatase etc.) was associated with treatment. Plasma creatinine showed a significant increase during use but the mean level remained within the normal range. In one patient the drug was stopped 2 days before the end of the 6-week course because a maculo-papular rash had developed over the forehead. 

Cimetidine would appear to be a potentially useful drug. It needs further careful and extensive evaluation with particular attention to the detection of bone marrow depression, changes in creatinine levels and serum enzymes. Long-term safety must of course also be established. 

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