A 55-year-old female patient with hyperlipemia received atorvastatin calcium tablets 20 mg,once daily orally.Two years later,the patient's legs appeared ecchymosis with distending pain and numbness.Laboratory tests showed serum myoglobin 682 μg/L and creatine kinase 1 007 U/L.She had not received any other drugs during the same period.Atorvastatin-induced rhabdomyolysis was considered.Atorvastatin was stopped,and the patient received symptomatic and supportive treatment.Twenty days later,her symptoms disappeared and her serum myoglobin and creatine kinase level turned to normal.A gene test of SLCO1B1 C521T polymorphism of organic anion transporting polypeptides associated with statin-induced muscle injury was detected after rhabdomyolysis,and the result showed TT genotype (non-mutant genotype).This suggested that the SLCO1B1 C521T genotypes could not predict the myotoxicity of statins accurately.

A 55-year-old female patient with hyperlipemia received atorvastatin calcium tablets 20 mg,once daily orally.Two years later,the patient's legs appeared ecchymosis with distending pain and numbness.Laboratory tests showed serum myoglobin 682 μg/L and creatine kinase 1 007 U/L.She had not received any other drugs during the same period.Atorvastatin-induced rhabdomyolysis was considered.Atorvastatin was stopped,and the patient received symptomatic and supportive treatment.Twenty days later,her symptoms disappeared and her serum myoglobin and creatine kinase level turned to normal.A gene test of SLCO1B1 C521T polymorphism of organic anion transporting polypeptides associated with statin-induced muscle injury was detected after rhabdomyolysis,and the result showed TT genotype (non-mutant genotype).This suggested that the SLCO1B1 C521T genotypes could not predict the myotoxicity of statins accurately.

Objective To explore the effects of pharmaceutical intervention based on genotype detection on curative effect and safety in hospitalized patients receiving warfarin. Methods The medical records of patients hospitalized in the Department of Cardiology,First Hospital of Peking University whose dosages of warfarin were adjusted according to the results of CYP2C9*2,CYP2C9*3,vitamin K epoxide reductase complex subunit ( VKORC1 )G-1639A genotype testing from June 2013 to March 2014 ( experimental group ) and the patients received warfarin but did not carry the genotype testing( control group)from June to December 2012 were collected and analyzed retrospectively. The length of hospital stay, administration time of warfarin,proportion of patients whose international normalized ratio(INR)≥3. 0 had happened,incidence of bleeding associated with warfarin,INR values and warfarin dosage on discharging were compared between the patients in the two groups. The correlation of warfarin dosage on discharging and the suggested dosage proposed by clinical pharmacist,the above-mentioned parameters and the genotype in the experimental group were analyzed. Results There were 102 patients in the experimental group comprised 62 male and 40 female with average age of(63 ± 16)years(14-88). There were 140 patients in the control group comprised 89 male and 51 female with average age of( 64 ± 13 ) years( 21-85 ). The patients'primary diseases included auricular fibrillation,deep vein thrombosis,pulmonary embolism and renal vein thrombus,etc. There were no statistically significant difference between age and sexual distinction in the 2 groups. The average length of hospital stay and average administration time of warfarin in patients in the experimental group were obviously longer than those in the control group[(16. 7 ± 8. 4)d vs.(12. 6 ± 6. 0)d,(13. 2 ± 8. 2)d vs. (9. 9 ± 6. 1)d,all P <0. 001]. There were no statistically significant difference of the proportion of INR≥3. 0,incidence of bleeding associated with warfarin,and INR values on discharging between the 2 groups. The warfarin dosage on discharging in patients carried CYP2C9*1/ *3 (7 cases)were lower than those in the patients carried CYP2C9*1/ *1(95 cases)in the experimental group [(1. 79 ± 0. 57)mg/d vs.(3. 12 ± 1. 13)mg/d,P=0. 003]. The warfarin dosage on discharging in patients carried VKORC1-1639 GG(1 case)and VKORC1-1639GA(20 cases)were more than those in the patients carried VKORC1-1639AA(81 cases)in the experimental group[6. 00,(3. 55 ± 1. 63)mg/d vs.(2. 87 ± 0. 92)mg/d,P=0. 002]. The length of hospital stay and administration time of warfarin in patients who INR≥3. 0 were longer than those in the patients who INR<3. 0[(24. 7 ± 10. 9)d vs. (15. 2 ± 6. 9)d,(21. 8 ± 10. 9)d vs.(11. 6 ± 6. 4)d,all P<0. 001]and the dosages of warfarin on discharging was lower than that in the patients who INR<3. 0 in the experimental group[(2. 50 ± 1. 02)mg/d vs. (3. 13 ± 1. 15)mg/d, P=0. 042]. In the control group,the difference of length of hospital stay between the patients who INR≥3. 0 and <3. 0 was no statistically significant,the administration time of warfarin in patients who INR≥3. 0 was longer that in the patients who INR <3. 0[(12. 6 ± 6. 5)d vs. (9. 3 ± 5. 8)d,P=0. 015],and the warfarin dosages on discharging was lower than that in the in the patients who INR <3. 0[(2. 49 ± 1. 17)mg/d vs. (3. 11 ± 0. 99)mg/d,P=0. 007]. The cases of fecal occult blood positive,slightly higher of red blood cell in the urine,and gingival bleeding were 8 and 14 in the experimental group and the control group,respectively. No severe bleeding was appeared in both groups. The bleeding was significantly correlated with the length of hospital stay and the administration time of warfarin in the control group(P=0. 001,P=0. 008). There was no correlation between bleeding and warfarin curative indexes in the experimental group. Conclusions The pharmaceutical intervention based on genotype detection can eliminate the effect of genetic factors on warfarin curative effect,avoid prolonging hospitalization caused by adjusting the dose repeatedly,and have a positive role in determination of warfarin maintenance dose. The pharmaceutical intervention has no effect on safety. It is suggested that the patient who receives warfarin anticoagulant therapy should do the genotype detection.

Objective To understand occurrence of bleeding related to drug interactions in patients who received combined treatment with warfarin and other drugs in Department of Cardiovascular Medicine and investigate control measures.Methods The data of inpatients using warfarin in the Department of Cardiovascular Medicine,Peking University First Hospital from January 2012 to June 2013 were collected and analyzed retrospectively.The conditions of concomitant drugs and occurrence of bleeding possibly caused by drug interactions were recorded and the drugs which were commonly used in the Department were screened.Results A total of 141 patients were enrolled including 90 men aged from 21 to 83 years with an average age of (63 ± 13) years and 51 women aged from 43 to 85 years with an average age of (65 ± 11)years.Most protopathy was atrial fibrillation which accounted for 79.4％ (112 cases).Of the 141 patients,there were 14 cases (9.9％) of slight bleeding possibly because of drug interactions including 5 cases of stool occult blood,3 cases of dermal ecchymosis and 1 case had each of the following:operative wound bleeding,oral mucosal bleeding and blood in phlegm,colporrhagia,epistaxis,hematuresis,and gum bleeding.The occurrence of bleeding in the 14 patients involved totally 9 kinds of drugs containing low molecular weight heparin (related to 9 cases),atorvastatin (related to 6 cases),amiodarone (related to 4 cases),acarbose (related to 3 cases),aspirin (related to 4 cases),propafenone (related to 3 cases),omeprazole (related to 2 cases),clopidogrel (related to 2 cases),and moxifloxacin (related to 1 case) and,of them,the highest occurrence was due to low molecular weight heparin,which accounted for 64.2％.In the 9 kinds of drugs in the 141 patients,low molecular weight heparin had the highest concomitant frequency combined with warfarin accounted for 73.1％ (103/141) and moxifloxacin had the highest bleeding incidence accounted of 1/5.Conclusions Bleeding may be caused by drug reactions due to combination therapy with warfarin and parts of clinical common cardiovascular drugs.Positive clinical pharmaceutical care of warfarin will be of great importance in prevention of bleeding.

Objective To explore the effects of pharmaceutical intervention based on genotype detection on curative effect and safety in hospitalized patients receiving warfarin. Methods The medical records of patients hospitalized in the Department of Cardiology,First Hospital of Peking University whose dosages of warfarin were adjusted according to the results of CYP2C9*2,CYP2C9*3,vitamin K epoxide reductase complex subunit ( VKORC1 )G-1639A genotype testing from June 2013 to March 2014 ( experimental group ) and the patients received warfarin but did not carry the genotype testing( control group)from June to December 2012 were collected and analyzed retrospectively. The length of hospital stay, administration time of warfarin,proportion of patients whose international normalized ratio(INR)≥3. 0 had happened,incidence of bleeding associated with warfarin,INR values and warfarin dosage on discharging were compared between the patients in the two groups. The correlation of warfarin dosage on discharging and the suggested dosage proposed by clinical pharmacist,the above-mentioned parameters and the genotype in the experimental group were analyzed. Results There were 102 patients in the experimental group comprised 62 male and 40 female with average age of(63 ± 16)years(14-88). There were 140 patients in the control group comprised 89 male and 51 female with average age of( 64 ± 13 ) years( 21-85 ). The patients'primary diseases included auricular fibrillation,deep vein thrombosis,pulmonary embolism and renal vein thrombus,etc. There were no statistically significant difference between age and sexual distinction in the 2 groups. The average length of hospital stay and average administration time of warfarin in patients in the experimental group were obviously longer than those in the control group[(16. 7 ± 8. 4)d vs.(12. 6 ± 6. 0)d,(13. 2 ± 8. 2)d vs. (9. 9 ± 6. 1)d,all P <0. 001]. There were no statistically significant difference of the proportion of INR≥3. 0,incidence of bleeding associated with warfarin,and INR values on discharging between the 2 groups. The warfarin dosage on discharging in patients carried CYP2C9*1/ *3 (7 cases)were lower than those in the patients carried CYP2C9*1/ *1(95 cases)in the experimental group [(1. 79 ± 0. 57)mg/d vs.(3. 12 ± 1. 13)mg/d,P=0. 003]. The warfarin dosage on discharging in patients carried VKORC1-1639 GG(1 case)and VKORC1-1639GA(20 cases)were more than those in the patients carried VKORC1-1639AA(81 cases)in the experimental group[6. 00,(3. 55 ± 1. 63)mg/d vs.(2. 87 ± 0. 92)mg/d,P=0. 002]. The length of hospital stay and administration time of warfarin in patients who INR≥3. 0 were longer than those in the patients who INR<3. 0[(24. 7 ± 10. 9)d vs. (15. 2 ± 6. 9)d,(21. 8 ± 10. 9)d vs.(11. 6 ± 6. 4)d,all P<0. 001]and the dosages of warfarin on discharging was lower than that in the patients who INR<3. 0 in the experimental group[(2. 50 ± 1. 02)mg/d vs. (3. 13 ± 1. 15)mg/d, P=0. 042]. In the control group,the difference of length of hospital stay between the patients who INR≥3. 0 and <3. 0 was no statistically significant,the administration time of warfarin in patients who INR≥3. 0 was longer that in the patients who INR <3. 0[(12. 6 ± 6. 5)d vs. (9. 3 ± 5. 8)d,P=0. 015],and the warfarin dosages on discharging was lower than that in the in the patients who INR <3. 0[(2. 49 ± 1. 17)mg/d vs. (3. 11 ± 0. 99)mg/d,P=0. 007]. The cases of fecal occult blood positive,slightly higher of red blood cell in the urine,and gingival bleeding were 8 and 14 in the experimental group and the control group,respectively. No severe bleeding was appeared in both groups. The bleeding was significantly correlated with the length of hospital stay and the administration time of warfarin in the control group(P=0. 001,P=0. 008). There was no correlation between bleeding and warfarin curative indexes in the experimental group. Conclusions The pharmaceutical intervention based on genotype detection can eliminate the effect of genetic factors on warfarin curative effect,avoid prolonging hospitalization caused by adjusting the dose repeatedly,and have a positive role in determination of warfarin maintenance dose. The pharmaceutical intervention has no effect on safety. It is suggested that the patient who receives warfarin anticoagulant therapy should do the genotype detection.

Objective To understand occurrence of bleeding related to drug interactions in patients who received combined treatment with warfarin and other drugs in Department of Cardiovascular Medicine and investigate control measures.Methods The data of inpatients using warfarin in the Department of Cardiovascular Medicine,Peking University First Hospital from January 2012 to June 2013 were collected and analyzed retrospectively.The conditions of concomitant drugs and occurrence of bleeding possibly caused by drug interactions were recorded and the drugs which were commonly used in the Department were screened.Results A total of 141 patients were enrolled including 90 men aged from 21 to 83 years with an average age of (63 ± 13) years and 51 women aged from 43 to 85 years with an average age of (65 ± 11)years.Most protopathy was atrial fibrillation which accounted for 79.4％ (112 cases).Of the 141 patients,there were 14 cases (9.9％) of slight bleeding possibly because of drug interactions including 5 cases of stool occult blood,3 cases of dermal ecchymosis and 1 case had each of the following:operative wound bleeding,oral mucosal bleeding and blood in phlegm,colporrhagia,epistaxis,hematuresis,and gum bleeding.The occurrence of bleeding in the 14 patients involved totally 9 kinds of drugs containing low molecular weight heparin (related to 9 cases),atorvastatin (related to 6 cases),amiodarone (related to 4 cases),acarbose (related to 3 cases),aspirin (related to 4 cases),propafenone (related to 3 cases),omeprazole (related to 2 cases),clopidogrel (related to 2 cases),and moxifloxacin (related to 1 case) and,of them,the highest occurrence was due to low molecular weight heparin,which accounted for 64.2％.In the 9 kinds of drugs in the 141 patients,low molecular weight heparin had the highest concomitant frequency combined with warfarin accounted for 73.1％ (103/141) and moxifloxacin had the highest bleeding incidence accounted of 1/5.Conclusions Bleeding may be caused by drug reactions due to combination therapy with warfarin and parts of clinical common cardiovascular drugs.Positive clinical pharmaceutical care of warfarin will be of great importance in prevention of bleeding.