Zocil

• Intermittent Claudication:
• Approved for the treatment of intermittent claudication due to peripheral arterial disease (PAD) to improve walking distance and reduce symptoms of leg pain.
• Off-label / Clinically Accepted Uses:
• Secondary prevention of stroke and transient ischemic attacks (when combined with aspirin or other antiplatelets)
• Prevention of restenosis after peripheral or coronary artery interventions (in selected cases)
• Management of symptoms in other forms of chronic arterial insufficiency (less common)

• Adults:
• Recommended dose: 100 mg orally twice daily (morning and evening, approximately 12 hours apart)
• Take on an empty stomach (1 hour before or 2 hours after meals) to enhance absorption
• Treatment duration: Individualized based on response; long-term therapy may be required for PAD symptom control
• Elderly:
• Use with caution; start at recommended doses and monitor for side effects
• Pediatrics:
• Safety and efficacy not established; use not recommended
• Renal Impairment:
• Mild to moderate impairment: no dose adjustment
• Severe impairment: use with caution; limited data available
• Hepatic Impairment:
• Contraindicated in severe hepatic impairment (Child-Pugh C)
• Use with caution in mild to moderate hepatic impairment

Cilostazol is a selective phosphodiesterase type 3 (PDE3) inhibitor that increases intracellular cyclic adenosine monophosphate (cAMP) in platelets and vascular smooth muscle cells. This leads to inhibition of platelet aggregation and vasodilation of arterial vessels. Increased cAMP causes relaxation of vascular smooth muscle, improving blood flow and oxygen delivery to ischemic tissues, thereby relieving symptoms of intermittent claudication. The drug also inhibits vascular smooth muscle proliferation, which may contribute to its vascular protective effects.

• Absorption: Rapidly absorbed after oral administration; bioavailability approximately 60% due to first-pass metabolism
• Peak Plasma Concentration: 1–2 hours post-dose
• Distribution: Highly protein-bound (~95%) primarily to albumin
• Metabolism: Extensively metabolized in the liver mainly via CYP3A4 and CYP2C19 enzymes to active metabolites
• Elimination: Metabolites excreted primarily via feces (about 60%) and urine (about 30%)
• Half-life: Approximately 11–13 hours for parent drug; active metabolites have longer half-lives supporting twice-daily dosing

• Pregnancy:
• Classified as Category C by the FDA
• Animal studies have shown adverse effects on fetal development at high doses; no adequate human studies
• Use only if potential benefits justify risks
• Lactation:
• Unknown whether cilostazol is excreted in human breast milk
• Caution advised; breastfeeding not recommended during therapy

• Primary Class: Antiplatelet Agent
• Subclass: Phosphodiesterase III inhibitor; Vasodilator

• Known hypersensitivity to cilostazol or any component of the formulation
• Heart failure of any severity (due to increased mortality risk with PDE3 inhibitors)
• Active bleeding or bleeding disorders
• Pregnancy and breastfeeding (unless benefit outweighs risk)
• Severe hepatic impairment (Child-Pugh C)
• Concurrent use with strong CYP3A4 inhibitors without dose adjustment

• Heart Failure Risk: Cilostazol is contraindicated in patients with any degree of heart failure
• Bleeding Risk: Use cautiously in patients with bleeding tendencies or on anticoagulants
• Monitor for Signs of Bleeding: Gastrointestinal or intracranial hemorrhage may occur
• CYP3A4 and CYP2C19 Interactions: Monitor for altered drug levels and toxicity with interacting drugs
• Use Cautiously in Renal Impairment: Limited data in severe cases
• Potential for Headache and Palpitations: Patients should be advised about possible cardiovascular side effects
• Avoid Abrupt Discontinuation: May increase risk of thrombotic events

Common Side Effects:

• Headache
• Diarrhea
• Palpitations or tachycardia
• Dizziness
• Peripheral edema
• Abdominal pain or discomfort

Less Common / Rare:

• Bleeding events (gastrointestinal hemorrhage, epistaxis)
• Tachyarrhythmias
• Hypotension
• Rash or hypersensitivity reactions
• Thrombocytopenia (rare)

Severity: Side effects usually mild to moderate; headaches and palpitations often diminish with continued use

• CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin, ritonavir): Increase cilostazol plasma levels; increase risk of toxicity
• CYP3A4 Inducers (e.g., rifampin, carbamazepine): Decrease efficacy by lowering plasma concentrations
• CYP2C19 Inhibitors (e.g., omeprazole): May increase cilostazol levels moderately
• Anticoagulants and Antiplatelets: Additive bleeding risk
• Grapefruit Juice: May increase cilostazol concentration; avoid excessive intake
• Alcohol: No significant interaction, but caution with bleeding risk

• 2024 PAD Management Guidelines (AHA/ACC):
• Cilostazol is reaffirmed as a first-line pharmacologic agent to improve walking distance in intermittent claudication
• Emphasize contraindication in heart failure patients
• Cautious use recommended in patients on multiple antithrombotic therapies
• 2023 FDA Safety Communication:
• No new safety concerns; reminder to monitor for bleeding and heart failure symptoms

• Store at 20°C to 25°C (68°F to 77°F)
• Protect from moisture and light
• Keep in tightly closed container
• Keep out of reach of children
• Do not freeze