Warfarin Sodium Tablets

SummaryThe effect of the administration of warfarin sodium (Coumadin®) on the duration of platelet aggregation in vitro was studied. Coumadin was given for 4 consecutive days to 10 healthy adults who were followed over a period of 9 days. The duration of adenosine diphosphate-induced platelet aggregation in platelet-rich plasma, the prothrombin time, and the platelet count of platelet-rich plasma were measured. Four other healthy adults received placebos and participated in a double-blind study with those receiving Coumadin.Although administration of Coumadin caused a prolongation of the prothrombin time to 2 or 21/2 times the normal value, a decrease in the duration of platelet aggregation was not observed. In most individuals who received Coumadin an increase in the duration of platelet aggregation occurred. The effect of Coumadin on platelet aggregation was not consistently related to the prothrombin time or to the platelet count. In the placebo group there was a distinct relation between the duration of platelet aggregation and the platelet count in platelet-rich plasma.The mean increase in the duration of platelet aggregation when compared to the control value before medication with Coumadin was 37.7%. In the placebo group there was a mean increase of 8.4%. The difference between the two groups is significant (p <0.001). Increased duration of platelet aggregation also occurred in two individuals who received Coumadin over a period of 10 and 16 days respectively.

Download Full-text

Effect of Formulation and Process Variables on the Critical Quality Attributes of Warfarin Sodium Tablets

10.26226/morressier.57d6b2bbd462b8028d88cf36 ◽

2016 ◽

Author(s):

Akhtar Siddiqui

Keyword(s):

Quality Attributes ◽

Process Variables ◽

Critical Quality Attributes ◽

Warfarin Sodium

Download Full-text

Phenotyping of CYP 4501A2 Activity by Total Overnight Salivary Caffeine Assessment (TOSCA) in Patients on Warfarin Treatment: A Cross-Sectional Study

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029617733040 ◽

2017 ◽

Vol 24 (6) ◽

pp. 928-935 ◽

Cited By ~ 1

Author(s):

Giovanni Tarantino ◽

Domenico Capone ◽

Paola Contaldi ◽

Adriana Gianno ◽

Mosca Teresa ◽

...

Keyword(s):

Adverse Events ◽

Drug Concentration ◽

Ethical Issues ◽

Single Point ◽

Warfarin Dose ◽

Individual Variability ◽

Bleeding Complications ◽

Close Monitoring ◽

Cross Sectional ◽

Warfarin Sodium

Warfarin is an oral anticoagulant, commonly used for primary and secondary prevention of venous and arterial thromboembolic events. The drug is characterized by narrow therapeutic index, widespread individual variability in clinical response, and high rates of adverse events, particularly bleeding complications. For these reasons, a close monitoring of the dosage, using the frequent assessment of coagulation status by means of International Normalized Ratio value, is mandatory. Warfarin is metabolized by hepatic cytochrome P-450. High CYP 450 activity may lead to low drug concentration and requires high warfarin doses to reach efficacy; conversely, low CYP 450 activity is responsible for high drug concentration and needs for low doses to avoid potential toxicity risks. The major isoforms of CYP involved in the metabolism of warfarin sodium are CYP1A2 (for the R-warfarin) and CYP2C9 (for the S-warfarin). The probes for testing CYP1A2 are phenacetin and caffeine while for CYP2C9 tolbutamide. Although S-warfarin has major activity, it was decided to exclude its phenotyping for ethical issues, being mandatory to use a drug (tolbutamide). Instead, it was chosen to test the 1A2 isoform, as the activity of the latter isoform could be investigated by using caffeine contained in the caffeinated beverages. Specifically, a single-point concentration of salivary caffeine (total overnight salivary caffeine assessment [TOSCA]) after an overnight period of the caffeinated beverages abstinence was utilized. In the present study, 75 nonsmoker patients regularly receiving warfarin sodium were enrolled. The results have showed a significant association of the warfarin dose with TOSCA values (coefficient = –0.15, standard error = 0.04, 95% confidence interval = –0.24 to –0.06, t = –3.23, P = .002). In conclusion, the phenotyping of CYP1A2 by TOSCA could be useful, if further proven, to help manage patients on warfarin in order to lessen severe adverse events.

Download Full-text