Cilostazolum

Uses

Cilostazolum is used for the reduction of symptoms of intermittent claudication, as used by an increased walking distance.

Cilostazolum is also used to associated treatment for these conditions: Intermittent Claudication

How Cilostazolum works

Cilostazolum and several of its metabolites are cyclic AMP (cAMP) phosphodiesterase III inhibitors (PDE III inhibitors), inhibiting phosphodiesterase activity and suppressing cAMP degradation with a resultant increase in cAMP in platelets and blood vessels, leading to inhibition of platelet aggregation and vasodilation.

Dosage

Cilostazolum dosage

The recommended dosage of Cilostazolum is 100 mg bid, taken at least half an hour before or two hours after breakfast and dinner.

A dose of 50 mg bid should be considered during coadministration of Fluconazole, Ketoconazole, Itraconazole, Erythromycin, Clarithromycin, Fluvoxamine, Fluoxetine, Nefazodone, Sertraline and Diltiazem.

Side Effects

The most common side effects are headache, diarrhoea, vomiting, leg cramps, rash etc. The less frequent side effects are anorexia and edema.

Toxicity

Information on acute overdosage with cilostazol in humans is limited. The signs and symptoms of an acute overdose can be anticipated to be those of excessive pharmacologic effect: severe headache, diarrhea, hypotension, tachycardia, and possibly cardiac arrhythmias. The oral LD₅₀ of cilostazol is >5.0 g/kg in mice and rats and >2.0 g/kg in dogs.

Precaution

Cilostazolum should be used with caution in patients with any degree of heart failure. There is no information with respect to the efficacy or safety of the concurrent use of Cilostazolum and Clopidogrel.

Interaction

Co-admin with drugs that affect CYP3A4 (erythromycin, other macrolides, diltiazem) or CYP2C19 (omeprazole) may influence the pharmacokinetics of cilostazol.

Food Interaction

• Avoid grapefruit products.
• Take on an empty stomach. A high fat meal will increase absorption.

[Moderate] GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of cilostazol.

The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

The extent and clinical significance are unknown.

Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Until more information is available, the manufacturer recommends avoiding consumption of grapefruit juice during cilostazol therapy.

Orange juice is not expected to interact with cilostazol.

Cilostazolum Drug Interaction

Moderate: aspirin, aspirin, aspirin, aspirin, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, clopidogrel, clopidogrelUnknown: pregabalin, pregabalin, metoprolol, metoprolol, metoprolol, metoprolol, tiotropium, tiotropium, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol

Cilostazolum Disease Interaction

Major: bleeding, heart failureModerate: hepatic impairment, ischemic heart disease

Elimination Route

Cilostazolum is absorbed after oral administration. A high fat meal increases absorption, with an approximately 90% increase in C_max and a 25% increase in AUC. Absolute bioavailability is not known.

Half Life

11-13 hours.

Elimination Route

Cilostazolum is extensively metabolized by hepatic cytochrome P-450 enzymes, mainly 3A4, and, to a lesser extent, 2C19, with metabolites largely excreted in urine. Cilostazolum is eliminated predominately by metabolism and subsequent urinary excretion of metabolites. The primary route of elimination was via the urine (74%), with the remainder excreted in feces (20%). No measurable amount of unchanged cilostazol was excreted in the urine, and less than 2% of the dose was excreted as 3,4-dehydro-cilostazol. About 30% of the dose was excreted in urine as 4'-trans-hydroxy-cilostazol.

Pregnancy & Breastfeeding use

There are no adequate and well controlled studies in pregnant women. Transfer of Cilostazolum into milk has been reported in experimental animals. Because of the potential risk to nursing infants, a decision should be made to discontinue nursing or to discontinue Cilostazolum.

Contraindication

Cilostazolum is contraindicated in patients with congestive heart failure of any severity. Cilostazolum is also contraindicated in patients with known or suspected hypersensitivity to any of its components.

Special Warning

Paediatric use: The safety and effectiveness of Cilostazolum in paediatric patients have not been established.

Acute Overdose

Severe headache, diarrhoea, hypotension, tachycardia, and possibly cardiac arrhythmias. Careful observation and supportive treatment are recommended.

Storage Condition

Store in a cool & dry place, protected from light and moisture

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