Vitamin interactions with warfarin

All quinolones interact with multivalent cations, forming chelation complexes resulting in reduced absorption. Major offenders are antacids vitamins containing calcium and iron can also be problematic. All fluoroquinolones interact with warfarin, didanosine (ddi), and phenytoin, resulting in decreased absorption or metabolism. Ciprofloxacin and other second-generation drugs interact with theophylline by decreasing its clearance, which leads to theophylline toxicity. 

None of these interactions is very well documented, and their clinical relevance is unclear. Note that vitamin K in food commonly interacts with warfarin, and these interactions are discussed in Coumarins and related drugs + Foods Vitamin Kj-rich , p.409. See also cranberry juice , (p.398), enteral and parenteral nutrition , (below), grapefruit juice , (p.411), mango , (p.408) and soya bean products , (p.408). 

Drugs that may interact with orlistat include cyclosporine, fat-soluble vitamins, pravastatin, and warfarin. 

The resultant modified E residues are gamma-carboxyglutamate (gla). This process is most clearly understood for factor II, also called preprothrombin. Prothrombin is modified pre-prothrombin. The gla residues are effective calcium ion chelators. Upon chelation of calcium, prothrombin interacts with phospholipids in membranes and is proteolysed to thrombin through the action of activated factor X (Xa). Dining the carboxylation reaction reduced hydroquinone form of vitamin K is converted to a 2,3-epoxide form. The regeneration of the hydroquinone form requires an uncharacterized reductase. This latter reaction is the site of action of the dicumarol-based anticoagulants such as warfarin. 

An interaction of warfarin with a nutritional supplement containing vitamin K has been reported (41). 

Warfarin disrupts the recycling of vitamin K epoxide form to active vitamin K. This results in depletion of available vitamin K stores, and eventually to lack of activation of vitamin K-de-pendent clotting factors—particularly factors II, VII, IX and X (recall that vitamin K is converted to an inactive epoxide form after interaction with platelet factors, and must be recycled" back to its active form in the liver [see Figure]). 

The possible case of an interaction with smokeless tobacco was attributed to the very high vitamin-K , (p.458), content of tobacco resulting in relative warfarin resistance. However, there were two previous DSTR spikes in this patient, which were attributed to dietary changes, an explanation that seems unlikely if there was a high background vitamin K intake from the tobacco. This case is therefore unclear. 

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. 

Drug/Food interactions Vitamin K-rich vegetables may decrease the anticoagulant effects of warfarin by interfering with absorption. Minimize consumption of vitamin K-rich foods (eg, spinach, seaweed, broccoli, turnip greens) or nutritional supplements. Mango has been shown to increase warfarin s effect. 

Coenzyme Q10 shares a structural similarity with vitamin K, and an interaction has been observed between coenzyme Q10 and warfarin. Coenzyme Q10 supplements may decrease the effects of warfarin therapy. This combination should be avoided or very carefully monitored. 

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