Warfarin administration

Partially responsible for inhibition of the extrinsic pathway. Inactivates factors V and VIII and promotes fibrinolysis. Activity declines following warfarin administration. cofactor to accelerate the anticoagulant activity of protein C. Decreased levels occur following warfarin administration. ... 

Argatroban is a small molecule thrombin inhibitor that is FDA-approved for use in patients with HIT with or without thrombosis and coronary angioplasty in patients with HIT. It, too, has a short half-life, is given by continuous intravenous infusion, and is monitored by aPTT. Its clearance is not affected by renal disease but is dependent on liver function dose reduction is required in patients with liver disease. Patients on argatroban will demonstrate elevated INRs, rendering the transition to warfarin difficult (ie, the INR will reflect contributions from both warfarin and argatroban). (INR is discussed in detail in the discussion of warfarin administration.) A nomogram is supplied by the manufacturer to assist in this transition. 

Drug Interactions Increased prothrombin time after warfarin administration Phenytoin Cyclosporine Tolbutamide Tacrolimus Glyburide Glipizide Rifampin Cisapride Terfenadine Astemizole Theophylline ... 

Figure 2 The half-life of the oral anticoagulant warfarin is shortened and its clearance increased when given as a single dose (1.5 mg/kg) before (o) and while ( ) subjects have taken the enzyme inducer rifampin 600 mg daily for 3 days prior to and 10 days following warfarin administration. The peak and duration in elevation of the prothrombin time, a measure of the anticoagulant response, are both decreased when rifampin is coadministered. Source From Ref. 6.

An alternative model, including a lag-time to allow for distributional effects embedded in the observed time delay of the onset of the effect after warfarin administration, was published by Pitsui et al. (1993). Setting the baseline value of clotting factor activity in the absence of warfarin (P0) to a fixed mean of three predose measurements, the program can estimate that parameter. 

The classic vitamin K antagonist is warfarin. Warfarin acts by blocking the vitamin K reductase enzymes required to regenerate active vitamin K (see Fig. 45.5). This results in reduced y-carboxylation of Factors II, VII, IX, and X. In the absence of y-carboxylation, the factors cannot bind calcium nor form the complexes necessary for the coagulation cascade to be initiated. However, warfarin also blocks the activity of proteins S and C, so both blood clotting and the regulation of clotting are impaired by warfarin administration. 

In rabbits orally administered 4 g/kg daily dong quai and subcutaneously administered warfarin, an increase in prothrombin time was observed in a steady-state model of warfarin administration, whereas in a single-dose model, no significant changes in prothrombin time were observed. Dong quai alone did not produce any changes in prothrombin time (Lo et al. 1995). 

The pharmacological and/or adverse effects of a drug can be reversed by co-administration of drugs which compete for the same receptor. For example, an opioid receptor antagonist naloxone is used to reverse the effects of opiates. Drugs acting at the same site with opposite effects also can affect each other, e.g. the reduction in the anticoagulant effect of warfarin by vitamin K. 

Administration of zafirlukast and aspirin increases plasma levels of zafirlukast, When zafirlukast is administered with warfarin, there is an increased effect of the anti coagulant. Administration of zafirlukast and theophylline or erythromycin may result in a decreased level of zafirlukast. Administration of montelukast with other drugs has not revealed any adverse responses. Administration of montelukast with aspirin and NSAIDs is avoided in patients with known aspirin sensitivity. Administration of zileuton with propranolol increases the activity or the propranolol with theophylline increases serum theophylline levels and with warfarin may increase prothrombin time (PT). A prothrombin blood test should be done regularly in the event dosages of warfarin need to be decreased. 

Promoting an Optimai Response to Therapy Heparin preparations, unlike warfarin, must be given by the parenteral route, preferably SC or IV The onset of anticoagiilation is almost immediate after a single dose. Maximum effects occur witiiin 10 minutes of administration. Clotting time will return to normal witiiin 4 hours unless subsequent doses are given. 

The administration of cloflbrate to a patient taking warfarin will potentiate the anticoagulant effect of warfarin by displacing It from Its protein binding site (7). This Interaction will cause... 

Vitamin K is a fat-soluble vitamin cofactor for the activation of factors II, VII, IX, and X in the liver. Almost all neonates are vitamin K-deficient at as a result of (1) insignificant transplacental vitamin K crossover, (2) lack of colonization of the colon by vitamin K-producing bacteria, and (3) inadequate dietary vitamin K intake (especially in breast-fed infants because human milk contains less vitamin K than infant formula or cow s milk). Vitamin K-deficiency bleeding (VKDB) refers to bleeding attributable to vitamin K deficiency within first 6 months of life. It occurs in three general time frames early (0-24 hours), classic (1-7 days), and late (2-12 weeks). Early onset occurs rarely and usually is associated with maternal ingestion of anticonvulsants, rifampin, isoniazid, and warfarin. Classic vitamin K-dependent bleeding usually results from the lack of prophylactic vitamin K administration in... 

The dose of capecitabine begins at 1250 mg/m2 twice a day when used by itself lower doses are used often when it is given in combination with irinotecan or oxaliplatin or in patients with renal insufficiency. The dose should be taken on a full stomach with breakfast and dinner. Capecitabine administered with warfarin can result in significant increases in the patient s INR and requires close monitoring to prevent bleeding. The convenience of oral administration and an improvement in toxicity make capecitabine a useful alternative to IV 5-FU both by itself and incorporated into other regimens used in colon cancer. 

Orlistat reduces the absorption of fat-soluble vitamins. Daily intake of a multivitamin containing vitamins A, D, E, and K, as well as 3-carotene, is recommended. Patients should take the multivitamin 2 hours prior to or after the dose of orlistat.31 Since availability of vitamin K may decline in patients receiving orlistat therapy, close monitoring of coagulation status should occur with concomitant administration of warfarin.31 Administration of orlistat in conjunction with cyclosporine can result in decreased cyclosporine plasma levels. To avoid this interaction, cyclosporine should be taken 2 hours preceding or following the dose of orlistat. Additionally, cyclosporine levels should be monitored more frequently.31... 

Other potential adverse effects include impaired absorption of fat-soluble vitamins A, D, E, and K hypernatremia and hyperchloremia GI obstruction and reduced bioavailability of acidic drugs such as warfarin, nicotinic acid, thyroxine, acetaminophen, hydrocortisone, hydrochlorothiazide, loperamide, and possibly iron. Drug interactions may be avoided by alternating administration times with an interval of 6 hours or greater between the BAR and other drugs. 

Avoid jejunal administration of ciprofloxacin Monitor clinical response Adjust warfarin dose based on international normalized ratio... 

In summary, the adverse effects associated with the quinolones appear presently to be mild to moderate in severity and reversible upon discontinuation of therapy. Severe systemic adverse reactions are rare [62], It is suggested that the use of these agents should be avoided, as far as possible, in children and pregnant women and that caution be used in their administration to patients with a seizure disorder or those taking theophylline or warfarin [62]. Articles suggesting the appropriate clinical usage for these important antibacterials have appeared [64],... 

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