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Issues for surgery

Recurrence of symptoms associated with intermittent claudication if omitted.

Increased risk of bleeding if continued.

Advice in the perioperative period

Elective surgery 

Continue.

Consider checking FBC, especially if there is any unexplained bleeding/bruising or other signs of blood dyscrasias (e.g., pyrexia, sore throat). If there is any evidence of clinical or laboratory haematological abnormalities, discuss with Haematologist.

EXCEPT:

• Procedures with high risk of bleeding or complications of bleeding (e.g., spinal surgery, some ophthalmological and neurosurgical procedures) or neuraxial anaesthesia, consider stopping 3 – 5 days before surgery – also see Perioperative considerations and Further information.

Emergency surgery 

For high-risk bleeding procedures: If there is insufficient time to follow the advice above, be aware of the potential for increased bleeding if patient has taken doses in the days leading up to surgery. Use of neuraxial anaesthesia should be based on a risk: benefit review – see Perioperative considerations and Further information.

Perioperative considerations

There is limited data on the use of neuraxial anaesthesia in the presence of cilostazol treatment and use of neuraxial anaesthesia in presence of cilostazol cannot be recommended.

Current recommendations indicate cilostazol should be stopped a minimum of 2 days before catheter insertion, and the next dose administered a minimum of 5 hours after block performance or catheter removal. See Further information.

Post-operative advice

Restart post-operatively when next dose is due.

Cilostazol should be taken 30 minutes before food. Administration with food has been associated with higher maximum plasma concentrations, which may increase the frequency of adverse reactions.

Monitor renal function post-operatively – treatment interruption may be necessary. Consult current product literature.

If there is any unexplained bleeding/bruising or other signs of blood dyscrasias (e.g., pyrexia, sore throat), check FBC. If there is any evidence of clinical or laboratory haematological abnormalities, cilostazol should be discontinued.

Interactions with common anaesthetic agents

None.

Interactions with other common medicines used in the perioperative period

Low molecular weight heparin (LMWH)

Both LWMH and cilostazol can cause bleeding; concurrent use might increase the risk of bleeding, and if the combination cannot be avoided, the patient should be monitored for signs of bleeding. Cilostazol is contraindicated with 2 or more antiplatelets or anticoagulants.

Non-steroidal anti-inflammatory drugs (NSAIDS)

Both NSAIDs and cilostazol can increase the risk of bleeding. No specific recommendations are made; monitor the patient for signs of bleeding if concomitant use is necessary.

Antimicrobials

Due to the inhibition of CYP3A4, concomitant use of macrolide antibiotics (i.e., erythromycin, clarithromycin) is predicted to increase the exposure to cilostazol, leading to an increase in adverse effects (e.g. headache, diarrhoea).

Whilst single prophylactic doses should not pose a problem, continued post-operative treatment may require monitoring for cilostazol's adverse effects. If symptoms occur, consider reducing the dose of cilostazol to 50mg twice daily.

Proton pump inhibitors

Due to the inhibition of CYP2C19, concomitant use of proton pump inhibitors is predicted to increase the exposure to cilostazol, leading to an increase in adverse effects (e.g., headache, diarrhoea). If symptoms occur, consider reducing the dose of cilostazol to 50mg twice daily.

Metoclopramide

Cilostazol might increase the exposure to metoclopramide; the manufacturer makes no recommendation, but it may be sensible to separate administration by several hours.

Further information

Cilostazol has reversible antiplatelet activity; however, in a clinical study of healthy subjects, it has not been shown to prolong bleeding times. Furthermore, when used in combination with either aspirin or clopidogrel, there was no significant additional increase in bleeding time or frequency of haemorrhagic events.

There is limited evidence about the perioperative management of cilostazol. Whilst the manufacturer suggests a 5-day cessation period, there is suggestion that for ophthalmological procedures, stopping cilostazol 3 days pre-operatively is sufficient (based on a quoted half-life of 11 – 13 hours). NB: the manufacturer of cilostazol states the half-life is 10.5 hours.

Furthermore, it has been proposed that a minimum of 2 days pre-operative cessation would also be sufficient in patients undergoing neuraxial anaesthesia.

Cilostazol is used for symptomatic relief only; it does not affect long-term disease progression. Hence, the risk of cessation is related only to the return of symptoms associated with intermittent claudication. However, this may impact on post-operative mobilisation, which may in turn affect recovery.

References

1. Ashken T, West S. Regional anaesthesia in patients at risk of bleeding. BJA Education. 2021; 21(3):84-94.
   
   
2. Baxter K, Preston CL (eds), Stockley's Drug Interactions (online). London: Pharmaceutical Press. https://www.medicinescomplete.com [Accessed 14th April 2025]
   
   
3. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com [Accessed on 14th April 2025]
   
   
4. Cilostazol. In: Brayfiled A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. https://www.medicinescomplete.com [Accessed 14th April 2025]
   
   
5. Gogarten W, Vandermeulen E, Van Aken H et al. Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology. Eur J Anaesthesiol. 2010; 27:999-1015 doi: 10.1097/EJA.0b013e32833f6f6f
   
   
6. Horlocker TT, Vandermeuelen E, Kopp SL et al. Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Fourth Edition). Reg Anesth Pain Med. 2018; 43:263-309 doi:10.1097/AAP.0000000000000763
   
   
7. Idrees S, Sridhar J, Kuriyan AE. Perioperative management of antiplatelet therapy in ophthalmic surgery. International Ophthalmology Clinics. 2020; 60(3):17-30
   
   
8. Nair A. Letter to Editor: Should we stop cilostazol before central neuraxial blockade? International Journal of Health & Allied Sciences. 2014; 3(1):73-4
   
   
9. National Institute for Health and Care Excellence. Cilostazol, naftidrofuryl oxalate, pentoxyfylline and inositol nicotinate for the treatment of intermittent claudication in people with peripheral arterial disease. Technology appraisal guidance TA223. Accessed via www.nice.org.uk 14/04/2025. Published 25th May 2011
   
   
10. Summary of Product Characteristics - Cilostazol 100 mg tablets. Mylan. Available via www.medicines.org.uk on 14th April 2025 [date of revision of the text December 2019]