Warfarin interactions with other drugs

Drug interactions Cimetidine is a CYP450 inhibitor and can inhibit the metabolism of phenytoin, warfarin, and theophylline. Famotidine, nizatidine, and ranitidine are unlikely to cause clinically significant drug interactions. All antagonists have the potential to interact with other drugs that require gastric acid for absorption (e.g., ketoconazole, itraconazole). 

Would protein binding interactions with other drugs (e.g., warfarin) be likely to occur with tricyclic antidepressants ... 

The manufacturers caution if enzyme-inducing anticonvulsants, particularly phenytoin, are used with modafiniL There is speculation, based on in vitro studies, about some possible interactions with other drugs, such as warfarin. Modafinil is an inducer of CYP3A4 and therefore may be expected to interact with substrates of this isoenzyme. 

Phenprocoumon has a long plasma half-life of 5 days and thus a duration of action that can last 7-10 days. On the other hand acenocoumarol has a half-life of 10-24 hours and therefore a shorter duration of action. The half-life of warfarin ranges from 25-60 hours and its the duration of action is 2-5 days. Both warfarin and phenprocoumon are highly protein bound and interactions may occur with other drugs that bind to albumin. 

Pharmacokinetics. Carbamazepine is extensively metabolised one of the main products, an epoxide (a chemically reactive form), has anticonvulsant activity similar to that of the parent drug but may also cause some of its adverse effects. The t) of carbamazepine falls from 35 h to 20 h over the first few weeks of therapy due to induction of hepatic enzymes that metabolise it as well as other drugs, including corticosteroids (adrenal and contraceptive), theophylline and warfarin. Cimetidine and valproate inhibit its metabolism. There are complex interactions with other antiepilepsy drugs, which constitute a reason for monodrug therapy. 

Drug Interactions. Levetiracetam neither inhibits nor indnces the CYP450, UGT, or epoxide hydrolase enzyme systems, and in vitro data predict a low potential for pharmacokinetic interactions. Levetiracetam does not appear to interact with other AEDs, warfarin, digoxin, or oral contraceptive drngs. ° ... 

Warfarin is heavily plasma protein-bound (> 97 percent). It therefore interacts with other protein-bound drugs (e.g., carbamazepine, phenytoin, and benzodiazepines) in that binding of warfarin to plasma proteins may displace bound drug that is administered as concurrent therapy. Thus, toxicity may result, due to elevated plasma levels, and the clearance rate of the drug may increase to compensate. 

After absorption, aprepitant is bound extensively to plasma proteins (>95%) it is extensively metabolized, primarily by hepatic CYP3A4, and is excreted in the stool its t is 9—13 hours. Aprepitant has the potential to interact with other substrates of CYP3A4, requiring adjustment of other drugs, including dexamethasone, methylprednisolone (whose dose may need to be reduced by 50%), and warfarin. Aprepitant is contraindicated in patients on cisapride (see above) or pimozide, in whom life-threatening ventricular tachyarrthmias has been reported. 

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. 

Pharmacokinetic interactions Preliminary evidence suggests that Saint-John s-wort induces the cytochrome oxidase enzyme isoform CYP3A4 (Ernst 1999). This raises the potential for pharmacokinetic interactions with drugs metabolized by the same enzyme. A few cases have been reported of reduced warfarin levels (Yue et al. 2000). Similar interactions have also been reported for concurrent use with digoxin, theophylline, and cyclosporin (Nebel et al. 1999 Ruschitzka et al. 2000 Johne et al. 1999). As with any other medication, potential interactions should be considered when taking a combination of drugs. 

Some chemical exposures may be hepatic enzyme inducers/inhibitors, altering the effects of drugs like warfarin. Some foods such as mono-amines, will cause reactions in patients given MAOIs grapefruit juice may interact with terfenadine and some other drugs. New diseases may cause problems heart failure causing reduced liver blood flow can reduce the metabolism of drugs like 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. 

Hypericum has been found to also interact with drugs metabolized via other pathways. For example, it decreases serum levels of digoxin, which is metabolized via the P-glycoprotein drug transporter, and reduces levels of theophylline and warfarin, which are metabolized via CYP1A2 and CYP2C9 pathways, respectively. It is possible that St. John s wort might also induce those enzymes via the steroid X receptor (Wentworth et ah, 2000). 

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