The gold standard for determining renal function is inulin clearance (GFR: glomerular filtration rate), but the determination of GFR is not usually performed in clinical practice because of the complexity of the procedure. Instead of the GFR, creatinine clearance is estimated by using the Cockcroft-Gault (CG) equation and estimated GFR (eGFR) for the Japanese population. Serum creatinine is affected by sex, muscle volume, and certain medications.Accurate estimation of renal function is necessary to adjust the dosage of renally excreted drugs. In this situation, eGFR (mL/min/1.73 m2) should not be used; rather, eGFR (mL/min) or CCr should be used except in the case of dosage planning where the units are indicated by mg/kg or mg/m2. In obese patients, the ideal body weight should be used in the CG equation.In regard to dosage adjustment based on CCr in package inserts, since almost all data in clinical trials had been obtained in western countries, serum creatinine determination was usually carried out using the Jaffe method. Estimation of CCr by the Jaffe method is close to the GFR. Even though CCr is mentioned in package inserts, actual measured GFR, eGFR ,or actual measured CCr×0.715 should be used as the indicators of renal function in Japan. Even though the contents of Japanese package inserts are the same as those of western countries, serious adverse effects from high-risk drugs might occur in Japan, because of the slight difference between the Jaffe method and the enzyme method of creatinine determination.When eGFR is determined to be high in thin elderly persons because of their low muscular volume, the determination of CCr by urine collection should be used, and the value should be multiplied by 0.715. GFR estimation using cystatin C is also useful. A high GFR due to augmented renal clearance is sometimes observed, particularly in young patients receiving vasoactive agents or transfusions with the systemic inflammatory response syndrome.
Because a large fraction of tiapride hydrochloride (tiapride) used to treat delirium and agitation is excreted unchanged in the urine, the dosage of tiapride should be reduced in patients with renal impairment or those undergoing hemodialysis (HD). The overdosing of tiapride results in oversedation and drowsiness as well as extrapyramidal symptoms due to its antidopaminergic action. Although 25 mg of tiapride, 1 to 2 times daily, is recommended for elderly individuals, its application in HD patients has not been specified. In this study, we therefore investigated the actual clinical application of tiapride to reveal its efficacy and safety. Subjects were 32 HD patients who were treated with tiapride for delirium in an inpatient setting between April 2002 and August 2012. As in elderly individuals, tiapride was highly effective and had a rapid onset of action in HD patients. However, 3 patients who received a single 25 mg dose were nonresponsive. Adverse reactions were observed in 7 of the 32 HD patients (≥5 on the Naranjo Adverse Drug Reaction [ADR] scale). The ADR group (n=7) was compared with the non-ADR group (n=25). The incidence of adverse reaction was significantly higher in patients who were given ≥37.5 mg/day of tiapride than in those given ≤25 mg/day (P<0.0001). In addition, the incidence of adverse reaction was more notable in patients given 0.6 mg/kg/day of tiapride than in those given ≤0.5 mg/kg/day (P=0.0049). Furthermore, a comparison of patients who had an early (≤3 days) and late (≥4 days) drug effect revealed that patients with an early effect had a higher incidence of adverse reactions (P=0.044). Some patients with adverse reactions were concurrently taking antipsychotics or anxiolytics, suggesting the synergy of concurrent medication on adverse reactions. The onset of drug action is early when used at 37.5 mg daily, and although it may be effective as a loading dose, we recommend ≤25 mg tiapride daily as a maintenance dose and ≤0.5 mg/kg/day to be safe. However, examination of a greater number of patients is needed to verify the efficacy and safety of tiapride.