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Cilostazol is a quinolinone-derivative medication used in the alleviation of the symptoms of intermittent claudication in individuals with peripheral vascular disease. It is manufactured by Otsuka Pharmaceutical Co. under the trade name Pletaal.
Although drugs similar to cilostazol have increased the risk of death in patients with congestive heart failure, studies of significant size have not addressed people without the disease.
Cilostazol is a phosphodiesterase 3 inhibitor with therapeutic focus on cyclic adenosine monophosphate (cAMP). It inhibits platelet aggregation and widens arteries (direct arterial vasodilator). Its main effects are dilation of the arteries supplying blood to the legs and decreasing platelet coagulation.
Contents
1 Mechanism
2 Clinical use
2.1 In people with heart failure
3 Adverse effects
4 Interactions
5 See also
6 References
7 External links
Mechanism
Cilostazol is a selective inhibitor of phosphodiesterase type 3 ( PDE 3 ) with therapeutic focus on increasing cAMP. An increase in cAMP results in an increase in the active form of protein kinase A (PKA), which is directly related with an inhibition in platelet aggregation. PKA also prevents the activation of an enzyme (myosin light-chain kinase) that is important in the contraction of smooth muscle cells, thereby exerting its vasodilatory effect.
Clinical use
Cilostazol is approved for the treatment of intermittent claudication. The typical dose is 100  mg twice a day. The effects may take as long as 3 months to be evident and has been shown to improve pain-free walking distance by 50%.
Cilostazol is also frequently used off-label, at the same dose, for treatment of intracranial atherosclerosis and secondary stroke prevention.
In people with heart failure
Cilostazol is dangerous for people with severe heart failure. Cilostazol has been studied in people without heart failure, without evidence of harm, but much more data would be needed to determine no risk exists. Although cilostazol would not be approvable for a trivial condition the Cardio-Renal Advisory Committee and FDA concluded that fully informed patients and physicians should be able to choose to use it to treat intermittent claudication. Patient and physician labeling will describe the basis for concern and the incomplete information available.
Adverse effects
Possible side effects of cilostazol use include headache (the most common), diarrhea, severe heat intolerance, abnormal stools, increased heart rate, and palpitations.
Interactions
Cilostazol is metabolized by CYP3A4 and CYP2C19, two isoenzymes of the cytochrome P450 system. Drugs that inhibit CYP3A4, such as itraconazole, erythromycin, ketoconazole, and diltiazem, are known to interact with cilostazol. The proton pump inhibitor omeprazole, a potent inhibitor of CYP2C19, increases exposure to the active metabolite of cilostazol.
A single report has been made of grapefruit juice possibly increasing the effects of cilostazol;
See also
Aripiprazole — an atypical antipsychotic with similar dihydroquinolinone core structure.

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