Drug Interactions between aspirin / caffeine / salicylamide and cilostazol

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.

Switch to consumer interaction data

MONITOR: Coadministration of cilostazol with other antiplatelet agents may produce additive pharmacodynamic effects resulting in increased inhibition of platelet function. In 12 healthy male volunteers, coadministration of cilostazol (100 mg twice a day for 10 days) and aspirin (325 mg once a day for the last 5 days of cilostazol administration) resulted in a 23% to 35% increase in inhibition of adenosine diphosphate (ADP)-induced ex vivo platelet aggregation compared to aspirin plus placebo. However, there was no additive or synergistic effect on arachidonic acid-induced platelet aggregation. Cilostazol, with or without aspirin, caused no changes in PT, aPTT, or bleeding time. Drug-related adverse events were generally mild, the most frequent being headache. Another study involving 21 patients with peripheral arterial disease also found no increase in bleeding time when cilostazol (100 mg twice a day) was added to clopidogrel (75 mg once a day), aspirin (325 mg once a day), or clopidogrel and aspirin combined, each for two weeks. The investigators concluded that cilostazol may be used with other platelet inhibitors. However, effects of long-term coadministration in the general population are unknown. During clinical trials, there was no apparent increase in the incidence of hemorrhagic adverse effects in 201 patients who received cilostazol with aspirin (75 to 325 mg daily for up to 137 days) compared to those who received placebo and equivalent doses of aspirin.

MANAGEMENT: Because of theoretical concerns regarding increased inhibition of platelet aggregation, cilostazol should be used cautiously with other antiplatelet agents.

Switch to consumer interaction data

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.

Switch to consumer interaction data