Cilostazol

(BAN, USAN, pINN)
Cilostazol Chemical formula
Synonyms: Cilostazolum; OPC-21; OPC13013. 6-[4-(1-Cyclohexyl-1Htetrazol-5-yl)butoxy]-3,4-dihydrocarbostyril.
Cyrillic synonym: Цилостазол.

💊 Chemical information

Chemical formula: C20H27N5O2 = 369.5.
CAS — 73963-72-1.

Pharmacopoeias.

In Jpn and US.

USP 31

(Cilostazol). White to off-white crystals. Practically insoluble in water; slightly soluble in alcohol and in methyl alcohol; freely soluble in chloroform. Store in airtight containers.

💊 Adverse Effects and Precautions

Adverse effects of cilostazol include headache, dizziness, palpitations, and diarrhoea; oedema, nausea and vomiting, other cardiac arrhythmias, chest pain, rhinitis, ecchymosis, and skin rashes have also been reported. Cardiovascular toxicity has been reported in animal studies of cilostazol, and prolonged oral use of other phosphodiesterase inhibitors for the treatment of heart failure has been associated with increased mortality. The use of cilostazol in patients with any degree of heart failure is therefore contra-indicated. It is also contra-indicated in patients with a known predisposition to bleeding, a history of ventricular arrhythmias, QT interval prolongation, severe renal impairment, or moderate to severe hepatic impairment. Cilostazol should be avoided or used in reduced doses in patients taking inhibitors of the cytochrome P450 isoenzymes CYP3A4 or CYP2C19 (see Interactions, below).

💊 Interactions

Cilostazol is extensively metabolised to active and inactive metabolites by cytochrome P450 isoenzymes, mainly CYP3A4 and to a lesser extent CYP2C19. Therefore use with other drugs that inhibit or are metabolised by these hepatic enzymes may result in changes in plasma concentrations of either drug and, possibly, adverse effects. Cilostazol should therefore be used with caution in patients taking drugs metabolised by these enzymes; in patients taking enzyme inhibitors it should be avoided or a reduced dose of 50 mg twice daily should be considered.

💊 Pharmacokinetics

Cilostazol is absorbed after oral doses and absorption is increased if taken with a high fat meal. Cilostazol is extensively metabolised in the liver by cytochrome P450 isoenzymes, mainly CYP3A4 and to a lesser extent CYP2C19, to both active and inactive metabolites; these are mainly excreted in the urine (74%) with the remainder in the faeces (20%). The active metabolites have apparent elimination half-lives of 11 to 13 hours. Cilostazol is 95 to 98% protein bound.
1. Woo SK, et al. Pharmacokinetic and pharmacodynamic modeling of the antiplatelet and cardiovascular effects of cilostazol in healthy humans. Clin Pharmacol Ther 2002; 71: 246–52.

💊 Uses and Administration

Cilostazol is a phosphodiesterase inhibitor with antiplatelet and vasodilating activity. It is used in the management of peripheral vascular disease. The usual dose of cilostazol for the reduction of symptoms of intermittent claudication is 100 mg orally twice daily, at least 30 minutes before or 2 hours after food; doses should be reduced in patients taking enzyme inhibitors (see Interactions, above). Response to treatment may occur in 2 to 4 weeks, but up to 12 weeks may be required. Cilostazol is under investigation for its antiplatelet effect after coronary stent implantation.
1. El-Beyrouty C, Spinler SA. Cilostazol for prevention of thrombosis and restenosis after intracoronary stenting. Ann Pharmacother 2001; 35: 1108–13
2. Goto S. Cilostazol: potential mechanism of action for antithrombotic effects accompanied by a low rate of bleeding. Atheroscler Suppl 2005; 6: 3–11
3. Matsumoto M. Cilostazol in secondary prevention of stroke: impact of the Cilostazol Stroke Prevention Study. Atheroscler Suppl 2005; 6: 33–40
4. Weintraub WS. The vascular effects of cilostazol. Can J Cardiol 2006; 22 (suppl B): 56B–60B
5. Dalainas I. Cilostazol in the management of vascular disease. Int Angiol 2007; 26: 1–7.

Peripheral vascular disease.

Intermittent claudication is a major feature of occlusive arterial disease of the lower limbs and is characterised by pain in the legs, which develops during exercise but usually disappears at rest. Many drugs have been used for symptom control, but none is of established benefit. Several randomised, double-blind studies1-4 have shown that cilostazol improves walking distances in patients with intermittent claudication, and one study5 suggested that it was more effective than pentoxifylline. Cilostazol may therefore have a role for symptom control in patients with intermittent claudication.6However, long-term benefit has not been assessed4 and, since patients with intermittent claudication are at high risk of other cardiovascular events, appropriate therapy to reduce cardiovascular risk is still required.
1. Money SR, et al. Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease. J Vasc Surg 1998; 27: 267–75
2. Beebe HG, et al. A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial. Arch Intern Med 1999; 159: 2041–50
3. Strandness DE, et al. Effect of cilostazol in patients with intermittent claudication: a randomized, double-blind, placebo-controlled study. Vasc Endovascular Surg 2002; 36: 83–91
4. Robless P, et al. Cilostazol for peripheral arterial disease. Available in The Cochrane Database of Systematic Reviews; Issu
1. Chichester: John Wiley; 2008 (accessed 19/03/08)
5. Dawson DL, et al. A comparison of cilostazol and pentoxifylline for treating intermittent claudication. Am J Med 2000; 109: 523–30
6. Crouse JR, et al. Clinical manifestation of atherosclerotic peripheral arterial disease and the role of cilostazol in treatment of intermittent claudication. J Clin Pharmacol 2002; 42: 1291–8.

💊 Preparations

USP 31: Cilostazol Tablets.

Proprietary Preparations

Arg.: Cibrogan; Cilostal; Cilovas; Licuagen; Pletaal; Policor; Trastocir; Trombonot; Braz.: Cebralat; Vasogard; Chile: Artesol; Ilostal; Kostal; Hong Kong: Pletaal; India: Cilodac; Pletoz; Stiloz†; Zilast; Indon.: Aggravan; Agrezol; Alista; Citaz; Naletal; Pletaal; Qital; Stazol; Jpn: Pletaal; Malaysia: Pletaal; Philipp.: Ciletin; Pletaal; Thai.: Pletaal; UK: Pletal; USA: Pletal.
Published January 13, 2019.