Drug Interactions between Emagrin and rivaroxaban

MONITOR CLOSELY: Concomitant use of rivaroxaban with other agents that alter hemostasis such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), platelet aggregation inhibitors, other anticoagulants, thrombolytic agents, or drugs that cause thrombocytopenia may increase the risk of bleeding. In patients receiving neuraxial anesthesia or spinal puncture, the risk of developing an epidural or spinal hematoma during rivaroxaban therapy may also be increased by the concomitant use of other drugs that affect coagulation. The development of epidural and spinal hematoma can lead to long-term neurological injury or permanent paralysis.

MANAGEMENT: Caution is recommended if rivaroxaban must be used with other agents that alter hemostasis. Patients should be monitored for increased anticoagulant effects and bleeding complications. In patients undergoing neuraxial intervention, coadministration of these agents should be approached with caution and only after thorough assessment of risks and benefits. Besides bleeding complications, patients should also be monitored frequently for signs and symptoms of neurologic impairment such as midline back pain, sensory and motor deficits (numbness or weakness in lower limbs), and bowel or bladder dysfunction.

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MONITOR: The combined use of low-dose or high-dose aspirin with other nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the potential for serious gastrointestinal (GI) toxicity, including inflammation, bleeding, ulceration, and perforation. Aspirin at anti-inflammatory dosages or higher may also decrease the plasma concentrations of many NSAIDs. The decreases have ranged from none or small (piroxicam, meloxicam, naproxen, tolmetin) to substantial (flurbiprofen, ibuprofen). However, the therapeutic response does not appear to be affected. Investigators theorize that aspirin may displace NSAIDs from plasma protein binding sites, resulting in increased concentration of unbound, or free, drug available for clearance. The increase in NSAID free fraction, and possibly some contributory anti-inflammatory effect from aspirin, may account for the lack of overall effect on therapeutic response.

MANAGEMENT: Caution is advised if aspirin, particularly at anti-inflammatory dosages, is used with other NSAIDs. Concomitant administration of NSAIDs is considered contraindicated or not recommended with aspirin at analgesic/anti-inflammatory dosages by many NSAID manufacturers. During concomitant therapy, patients should be advised to take the medications with food and to immediately report signs and symptoms of GI ulceration and bleeding such as abdominal pain, bloating, sudden dizziness or lightheadedness, nausea, vomiting, hematemesis, anorexia, and melena.

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GENERALLY AVOID: Theoretically, salicylates may potentiate the effects of anticoagulants and increase the risk of bleeding. Salicylates interfere with the action of vitamin K and induce a dose-dependent alteration in hepatic synthesis of coagulation factors VII, IX and X, occasionally increasing the prothrombin time. While these effects are generally slight for most salicylates (except aspirin) at recommended dosages, they may be of clinical significance when combined with the inhibitory effects of anticoagulants on the clotting cascade. Moreover, salicylates are known to cause dose-related gastrointestinal bleeding, which may be complicated by anticoagulant therapy.

MANAGEMENT: Until further data are available, products containing salicylates, especially if given chronically or in high dosages, should preferably be avoided in patients receiving anticoagulants. Close clinical and laboratory observation for bleeding complications is recommended if concurrent therapy is necessary. The same precaution should be observed with the use of salicylate-related agents such as salicylamide because of their structural and pharmacological similarities. Ambulatory patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools. Patients should also be counseled to avoid any other over-the-counter salicylate products.

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One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

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