Cilostazol reversibly inhibits phosphodiesterase III, resulting in vasodilation, inhibits platelets aggregation, and smooth muscle proliferation.
It is used to treat the following conditions:
- Symptomatic treatment and improvement in the walking distance in patients with intermittent arterial claudication
Other Off-Label Uses in Adults include:
- As an alternative agent in elective PCI with bare metal or drug eluting stent placement.
- Secondary prevention of non-cardioembolic ischemic stroke or transient ischemic attack (TIA).
- As an adjunct to aspirin and clopidogrel in the prevention of stent thrombosis and restenosis after coronary stent placement.
Cilostazol Dose in Adults
The dose of cilostazol in intermittent claudication:
- 100 mg orally twice daily in combination with aspirin or clopidogrel (in patients refractory to exercise therapy and smoking cessation.
- Treatment should be discontinued if the patient remains symptomatic after 3 months of therapy.
Off-label use in PCI (following elective stent placement):
- 100 mg twice daily in combination with aspirin or clopidogrel.
Note: Recommended only in patients with an allergy or intolerance to either aspirin or clopidogrel.
Off-label use in Secondary prevention of non-cardioembolic stroke or TIA:
- Oral: 100 mg twice daily.
Note: Clopidogrel or aspirin/extended-release dipyridamole is preferred over cilostazol.
Dose adjustment with concomitant medications:
- CYP2C19 inhibitors (eg, fluconazole, omeprazole, ticlopidine):
- Reduce cilostazol dose to 50 mg twice daily.
- Strong or moderate CYP3A4 inhibitors (eg, diltiazem, erythromycin, itraconazole, ketoconazole):
- Reduce cilostazol to 50 mg twice daily.
Cilostazol Dose in Childrens
Not recommended in children.
Pregnancy Risk Factor C
Cilostazol is not recommended for pregnant women.
- It should not be used in pregnant patients because of adverse reactions that have been shown in animal studies.
Cilostazol use during breastfeeding
- It is unknown whether cilostazol can be found in breastmilk.
- It is important to consider the risks and benefits of drug exposure for the baby when deciding whether to breastfeed.
Cilostazol Dose in Kidney Disease:
- No adjustment in dose has been recommended, however, it should be administered with caution in patients with moderate to severe renal impairment and patients on hemodialysis.
Cilostazol Dose in Liver Disease:
- No adjustment in dose has been recommended, however, it should be administered with caution in patients with moderate to severe hepatic impairment.
Common Side Effects of Cilostazol:
- Central nervous system:
- Headache
- Gastrointestinal:
- Diarrhea
- Abnormal stools
- Infection:
- Infection
- Respiratory:
- Rhinitis
Less Common Side Effects of Cilostazol:
- Cardiovascular:
- Palpitations
- Peripheral edema
- Tachycardia
- Atrial fibrillation
- Atrial flutter
- Cardiac arrest
- Cardiac failure
- Cerebral infarction
- Edema
- Facial edema
- Hypotension
- Myocardial infarction
- Nodal arrhythmia
- Orthostatic hypotension
- Supraventricular tachycardia
- Syncope
- Varicose veins
- Ventricular premature contractions
- Ventricular tachycardia
- Central nervous system:
- Dizziness
- Vertigo
- Anxiety
- Chills
- Insomnia
- Malaise
- Neuralgia
- Dermatologic:
- Ecchymoses
- Furunculosis
- Skin hypertrophy
- Urticaria
- Xeroderma
- Endocrine & metabolic:
- Albuminuria
- Diabetes mellitus
- Gout
- Hyperlipidemia
- Hyperuricemia
- Increased gamma-glutamyltransferase
- Gastrointestinal:
- Nausea
- Dyspepsia
- Abdominal pain
- Flatulence
- Anorexia
- Cholelithiasis
- Colitis
- Duodenal ulcer
- Duodenitis
- Esophageal hemorrhage
- Esophagitis
- Gastric ulcer
- Gastritis
- Gastroenteritis
- Gingival hemorrhage
- Hematemesis
- Melena
- Peptic ulcer
- Periodontal abscess
- Genitourinary:
- Cystitis
- Pelvic pain
- Urinary frequency
- Vaginal hemorrhage
- Vaginitis
- Hematologic & oncologic:
- Anemia
- Hemorrhage
- Hemorrhage (eye)
- Iron deficiency anemia
- Polycythemia
- Purpura
- Rectal hemorrhage
- Retroperitoneal hemorrhage
- Hypersensitivity:
- Tongue edema
- Neuromuscular & skeletal:
- Back pain
- Myalgia
- Arthralgia
- Bursitis
- Neck stiffness
- Ostealgia
- Ophthalmic:
- Amblyopia
- Blindness
- Conjunctivitis
- Diplopia
- Retinal
- Hemorrhage
- Otic:
- Otalgia
- Tinnitus
- Renal:
- Increased serum creatinine
- Respiratory:
- Pharyngitis
- Cough
- Asthma
- Epistaxis
- Hemoptysis
- Pneumonia
- Sinusitis
- Miscellaneous:
- Fever
Contraindication to Cilostazol include:
- Allergy or intolerance to cilostazol, any component of the formulation
- Any degree of heart failure.
Warnings and Precautions
- Cardiovascular effects:
- Cilostazol can cause tachycardia and palpitation. After initiating cilostazol therapy, monitor for the appearance of new cardiac symptoms or a systolic murmur. (Lost ventricular obstruction with sigmoid-shaped interventricular septum has been reported.
- Hematologic effects:
- Reversible cases may occur when thrombocytopenia, leukopenia or thrombocytopenia progress to agranulocytosis. Blood CBC should be monitored periodically.
- Hemostatic disorders:
- Cilostazol should be avoided in patients with a bleeding disorder.
- Cardiovascular disease [US Boxed Warning]
- Patients with a history of cirostazolemia should not take Cilostazol.Heart failure of any severityPatients who have had ischemic heart disease in the past may be more at risk of developing angina pectoris.
- Hepatic impairment:
- Patients with severe or moderate liver disease should be cautious.
- Renal impairment:
- Patients with severe renal impairment must be cautious when taking the drug.
- Elective surgery:
- Cilostazol should be stopped atleast 2 days prior to an elective surgery.
Cilostazol: Drug Interaction
Note: Drug Interaction Categories:
- Risk Factor C: Monitor When Using Combination
- Risk Factor D: Consider Treatment Modification
- Risk Factor X: Avoid Concomitant Use
Risk Factor C (Monitor therapy). |
|
| Antiplatelet Agents (e.g. P2Y12 inhibitors NSAIDs, SSRIs etc.) | May increase the antiplatelet effects of other Agents with Antiplatelet Properties. |
| Anticoagulants | Anticoagulants may be enhanced by agents with Antiplatelet properties. |
| Apixaban | Apixaban's toxic/adverse effects may be exacerbated by agents with Antiplatelet Properties. The risk of bleeding could be increased. Management: Take the time to carefully consider both the risks and the benefits of this combination, and keep an eye on it. |
| ARIPiprazole | CYP3A4 Inhibitors, Weak, may increase serum levels of ARIPiprazole. Monitoring for increased aripiprazole-pharmacologic effects is important. Aripiprazole dosage adjustments may be necessary depending on the indication and/or concomitant therapy. For more information, consult the full interaction monograph. |
| Bosentan | Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
| Cephalothin | Antiplatelet agents may increase the toxic/adverse effects of Cephalothin. In particular, bleeding risk may be increased. |
| Clofazimine | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Collagenase (Systemic) | Antiplatelet agents may increase the toxic/adverse effect of Collagenase Systemic. In particular, there may be an increase in the risk of bleeding and/or bruising at the injection site. |
| Moderate CYP3A4 Inducers | Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
| Dabigatran Etexilate | Antiplatelet properties may increase the anticoagulant effects of Dabigatran Etexilate. Agents with Antiplatelet Properties can increase serum levels of Dabigatran Etexilate. Clopidogrel is exempt from this mechanism. Management: Be aware of the risks and benefits and keep an eye on this combination. Canadian labeling suggests that you avoid prasugrel and ticagrelor. |
| Dasatinib | Agents with Antiplatelet Properties may increase the anticoagulant effects. Management: The drug interactions monographs for drugs listed as an exception to this monograph provide more information. |
| Deferasirox | Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
| Deoxycholic Acid | Antiplatelet agents may increase the toxic/adverse effects of Deoxycholic Acid. In particular, bleeding and bruising may increase in the treatment area. |
| Dofetilide | Dofetilide may be increased by CYP3A4 inhibitors (Weak). |
| Edoxaban | Antiplatelet agents may increase the toxic/adverse effects of Edoxaban. In particular, bleeding risk may be increased. |
| Erdafitinib | Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
| Erdafitinib | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Fat Emulsion (Fish oil-based) | Agents with Antiplatelet Property may have an adverse/toxic effect. |
| Flibanserin | Flibanserin may be increased by CYP3A4 inhibitors (Weak). |
| Fosaprepitant | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Glucosamine | Agents with Antiplatelet Properties may increase the antiplatelet effects. |
| Ibritumomab Tiuxetan | Antiplatelet agents may increase the toxic/adverse effects of Ibritumomab Tiuxetan. Both agents can cause impaired platelet function, which could lead to increased bleeding risk. |
| Ibrutinib | May increase the toxic/adverse effects of agents with Antiplatelet Property. |
| Inotersen | Agents with Antiplatelet Properties may increase the antiplatelet effects. |
| Ivosidenib | Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
| Larotrectinib | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Limaprost | Agents with Antiplatelet Properties may increase the antiplatelet effects. |
| Multivitamins/Fluoride (with ADE) | Agents with Antiplatelet Properties may increase the antiplatelet effects. |
| Multivitamins/Minerals (with ADEK, Folate, Iron) | Agents with Antiplatelet Properties may increase the antiplatelet effects. |
| Multivitamins/Minerals (with AE, No Iron) | Agents with Antiplatelet Properties may increase the antiplatelet effects. |
| NiMODipine | CYP3A4 Inhibitors, Weak may increase NiMODipine serum concentrations. |
| Obinutuzumab | Antiplatelet agents may increase the toxic/adverse effects of Obinutuzumab. In particular, there may be an increase in the risk of bleeding-related complications. |
| Omega-3 Fatty Acids | Agents with Antiplatelet Properties may increase the antiplatelet effects. |
| Palbociclib | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Pentosan Polysulfate Sodium | Agents with Antiplatelet Property may have an adverse/toxic effect. Concurrent use of these agents may increase the risk of bleeding. |
| Pentoxifylline | Agents with Antiplatelet Properties may increase the antiplatelet effects. |
| Prostacyclin Analogues | Agents with Antiplatelet Properties may increase the antiplatelet effects. |
| Riociguat | Cilostazol could increase the hypotensive effects of Riociguat. Riociguat should not be used in conjunction with nonselective PDE (PDE) inhibitors or PDE type 5 inhibitors. Although other types of PDE inhibitors may not be contraindicated but patients should be monitored for hypotension. |
| Rivaroxaban | Rivaroxaban may be enhanced by agents with Antiplatelet Properties. Management: Be aware of the risks and benefits and keep an eye on this combination. Canadian labeling suggests that you avoid prasugrel and ticagrelor. |
| Salicylates | Antiplatelet agents may increase the toxic/adverse effects of Salicylates. This could lead to an increase in bleeding risk. |
| Sarilumab | Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
| Siltuximab | Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
| Simeprevir | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Thrombolytic Agents | Agents with Antiplatelet Properties can enhance the anticoagulant effects of Thrombolytic Agents. |
| Tipranavir | Agents with Antiplatelet Properties may increase the antiplatelet effects. |
| Tocilizumab | Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
| Vitamin E (Systemic) | Agents with Antiplatelet Properties may increase the antiplatelet effects. |
Risk Factor D (Keep in mind therapy modification) |
|
| Cladribine | Increased serum levels of Cladribine may be caused by inhibitors of Equilibrative Nucleoside(ENT1) or Concentrative Nucleoside Transport Proteins (CNT3). Management: Avoid concurrent use of ENT1 and CNT3 inhibitors in the 4- to 5-day oral cladribine treatment cycles. Consider a reduction in dose or separation of CNT3 inhibitors if they are combined. |
| CYP2C19 inhibitors | Could increase serum Cilostazol concentrations. Treatment: Patients who are receiving inhibitors of CYP2C19 may be advised to reduce the cilostazol dosage to 50mg twice daily. |
| Strong CYP3A4 Inducers | May increase metabolism of CYP3A4 substrates (High Risk with Inducers). Management: You may consider a different drug to replace one of the interacting drugs. Some combinations might be contraindicated. Consult appropriate manufacturer labeling. |
| Moderate CYP3A4 inhibitors | Increased serum Cilostazol concentrations may occur. Management: Reduce the dose of cilostazol to 50mg twice daily for adult patients who are also taking moderate inhibitors of CYP3A. |
| Strong CYP3A4 inhibitors | Increased serum Cilostazol concentrations may occur. Treatment: Reduce the dose of cilostazol to 50mg twice daily for adult patients who are also taking strong inhibitors of CYP3A. |
| Dabrafenib | High risk of Inducers causing a decrease in serum CYP3A4 substrates. Management: If possible, seek alternatives to the CYP3A4 substrate. Concomitant therapy should be avoided if possible. Monitor the clinical effects of the substrate carefully (especially therapeutic effects). |
| Enzalutamide | High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Management: Avoid concurrent use of enzalutamide and CYP3A4 substrates with a narrow therapeutic index. You should exercise caution when using enzalutamide or any other CYP3A4 sub-substance. |
| Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry | Agents with Antiplatelet Property may have an adverse/toxic effect. Possible bleeding. Management: Avoid using combination medications whenever possible. Monitor for bleeding signs if you use this combination. Stop using herbal products that contain anticoagulant or Antiplatelet actions two weeks before any surgical, dental or invasive procedure. |
| Lomitapide | Lomitapide may be increased by CYP3A4 inhibitors (Weak). Management: Patients taking lomitapide 5 mg/day can continue to take this dose. Patients who are taking lomitapide 10mg/day or more must reduce their lomitapide dosage by half. You can then adjust the lomitapide dose to 30 mg/day for adults. |
| Lorlatinib | High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Management: Do not use lorlatinib concurrently with any CYP3A4 Substrates. Even a slight decrease in serum concentrations could cause therapeutic failure or serious clinical consequences. |
| MiFEPRIStone | High risk of Inhibitors causing an increase in serum concentrations of CYP3A4 substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid dihydroergotamine and ergotamine. |
| Mitotane | High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Treatment: Patients receiving mitotane may require significant adjustments in the dosage of CYP3A4 Substrates. |
| Pitolisant | High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates Management: Avoid combining pitolisant and a CYP3A4 substrat with a low therapeutic index. Pitolisant should not be combined with other CYP3A4 sub-substances. |
| St John's Wort | High risk of Inducers causing a decrease in serum CYP3A4 Substrates. Management: You may consider a different drug to replace one of the interacting drugs. Some combinations might be contraindicated. Consult appropriate manufacturer labeling. |
| Stiripentol | High risk of Inhibitors causing an increase in serum concentrations of CYP3A4 substrates. Management: Avoid stiripentol use with CYP3A4 Substrates that have a narrow therapeutic Index. This is to avoid adverse effects and toxicities. Monitoring of any CYP3A4 substrate that is used with stiripentol should be closely done. |
Risk Factor X (Avoid Combination) |
|
| Anagrelide | Might increase the toxic/adverse effects of Cilostazol. |
| Conivaptan | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Fusidic Acid (Systemic). | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Idelalisib | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Pimozide | Pimozide may be increased by CYP3A4 inhibitors (Weak). |
| Urokinase | Agents with Antiplatelet Property may increase the anticoagulant effects of Urokinase. |
Monitoring Parameters:
Monitor platelets and WBC counts at baseline and then periodically Monitor for the development of a new systolic murmur or cardiac symptoms.
How to take Cilostazol?
- Administer cilostazol 30 minutes before or 2 hours after meals (breakfast and dinner).
Mechanism of action of Cilostazol:
- Cilostazol, its metabolites, inhibit the enzyme phosphodiesterase 3.
- This causes an increase in cyclic AMP which leads to reversible inhibition platelet aggregation and vasodilation and inhibition of vascular smooth muscles cell proliferation.
The Onset of action may require up to 12 weeks for full effects. Improvement on walking distance may be noted in 2 to 4 weeks time.
95% to 98% of the drug is bound to proteins.
It is metabolized by the liver via CYP1A2 (minor), CYP2C19 (major), CYP2D6 (minor), and CYP3A4 (major).
Half-life elimination is 11 to 13 hours.
It is excreted mainly via Urine (74%) and feces (20%) as metabolites
International Brands of Cilostazol:
- Aggravan
- Agrezol
- Alista
- Angiovan
- Antaclast
- Artesol
- Bestazol
- Cebralat C
- Cibrogan
- Ciletin
- Cilo V
- Cilogrand
- Cilosol
- Cilost
- Cilostad
- Cilostal
- Cilostol
- Cilostop
- Cilovas
- Cilovitae
- Cilozek
- Cistazol
- Citakey
- Citaz
- Citazol
- Claudic
- Claudicat
- Claudine
- Clauter
- Clazol
- Cylozza-100
- Dilsatan
- Dilvas
- Ekistol
- Ilostal
- Inclaud
- Labista
- Licuagen
- Lostrazin
- Lozence
- Naletol
- Nibixada
- Pancil
- Pencil
- Pladizol
- Pladizole
- Plestazol
- Pletaal
- Pletal
- Pletoz
- Pleya
- Policor
- Qital
- Sadoxol
- Smizole
- Sollazon
- Stazol
- Stepcil
- Stiloz
- Trastocir
- Vasativ
- Vasocil
- Vasogard
- Vaxol
- Velyn
- Zilast
- Zocil
- [/bg_collapse]
Cilostazol Brands in Pakistan:
|
Cilostazole [Tabs 50 mg] |
|
| LABISTA | WILSHIRE LABORATORIES (PVT) LTD. |
| LOSTAZ | MATRIX PHARMA |
| PLATOR | DON VALLEY PHARMACEUTICALS (PVT) LTD. |
| PLETAAL | OTSUKA PAKISTAN LTD. |
| WALK-AID | WERRICK PHARMACEUTICALS |
|
Cilostazole [Tabs 100 mg] |
|
| CILOSTA | AMARANT PHARMACEUTICALS (PVT) |
| LABISTA | WILSHIRE LABORATORIES (PVT) LTD. |
| LOSTAZ | MATRIX PHARMA |
| PLATOR | DON VALLEY PHARMACEUTICALS (PVT) LTD. |
| PLETAAL | OTSUKA PAKISTAN LTD. |
| WALK-AID | WERRICK PHARMACEUTICALS |
 Injection.webp)