Co-administration of drugs that affect CYP3A4 (erythromycin and other macrolides , dilitiazem ) or CYP2C19 (omeprazole) has the potential to influence the pharmacokinetics of clistazol

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use

PLETAL safely and effectively. See full prescribing information for PLETAL. PLETAL? (cilostazol) tablets, for oral use.

Initial U.S. Approval: 1999

LIST OF DRUGS DURING 2007

New drugs approved For Marketing by Drug Controller General of India(DCGI )                                   during the period January 1988 to November 2014                                                                                  (Ref- IDMA Annual Publication 2015)

Cilostazol has been well tolerated in clinical trials.

The most comon adverse recations are headache, diarrhea, abnormal stools, pain, infection, pharyngitis, rhinitis, peripheral edema, and nausea.

Adverse effects are generally mild to moderate in intensity, transcient or resolved after symptomatic treatment and rarely required treatment withdrawal.

None reported

Special precautions-

Patients with coronary heart disease, those receiving concomittant medications with inhibitors of CYP3A4 or CYP2C19

Initial U.S. Approval: 1999

Indication-

Intermittant claudication

Dosage-

100mg twice daily 30 minutes before or 2 hours after breakfast and evening meal

Children- not recommendedIntermittant claudication

Stroke

         EVIDENCE BASED MEDICINE (MIMS -April 2003)

                 Stroke prevention

Comparative effectiveness of various interventions

PRIOR TO STROKE OR TRANSIENT ISCHAEMIC ACCIDENT (TIA)

Beneficial

1. Antiplatelet treatment
2. Cholestrerol reduction (for those patients who also have coronary heart disease)
3. Carotid endarterectomy (in patients with severe symptomatic carotid artery stenosis)

Unknown effectiveness

1. Cholesterol reduction (for patients without CHD)
2. Blood pressure reduction
3. Carotid endarterectomy (in patients with severe symptomatic carotid artery stenosis)
4. Catotid angioplasty

Likely to ineffective or even harmful

1. Oral anticoagulation

ATRIAL FIBRILLATION AND A PRIOR STROKE OR TIA

Beneficial

1. Oral anticoagulation
2. Aspirin for patients with contraindications to an anticoagulant

ATRIAL FIBRILLATION BUT NO OTHER MAJOR RISK FACTORS FOR STROKE

Likely to be beneficial

1. Oral anticoagulation
2. Aspirin for patients with contraindications to an anticoagulant

KEY POINTS

In patients with a prior stroke or TIA

1. Insufficient evidence to support routine blood presure reduction
2. Statins may prevent stroke in those with a history of CHD but evidence inconclusive in those with no history of CHD.
3. Routine use of prolonged anti-platelet treatment beneficial ( if no contraindication)
4. Aspirin 75mg daily as effective as higher doses. No evidence that any other antiplatelet regimen is definitely
    superior  in the prevention of vascular events. Clopidogrel or the combination of asprin and dipyridamole are safe
    and effective (but more costly) alternatives to aspirin
5. No evidence of benefit from anti-coagulation in patients in sinus rhythm, but an increased risk of serious bleeding
6. Carotid endarterectomy  reduces risk of major stroke in patients with severe carotid stenosis provided the risks of
    imaging and surgery are small. 
7. Percutaneous transluminal angioplastys role has not been evaluated adequately

In patients with atrial fibrillation and a pror stroke or TIA

1. Anticoagulants reduce risk of stroke, provided there is low risk of bleeding and careful monitoring
2. Aspirin reduces risk of stroke but less effectively than anticoagulants. These findings support the use of aspirin
    among patients with atrial fibrillation and contra-indication to anticoagulants

In patients with atrial fibrillation but neither major risk factors for stroke

1. Anticoagulants are of net benefit, if low risk of bleeding and careful monitoring
2. Aspirin is a reasonable alternative in patients with contra-indications to anticoagulants

 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information)

Advise the patient:

• to take PLETAL at least one-half hour before or two hours after food. • to discuss with their doctor before taking any CYP3A4 or CYP2C19 inhibitors (e.g., omeprazole)

• that the beneficial effects of PLETAL on the symptoms of intermittent claudication may not be immediate. Although the patient may experience benefit in 2 to 4 weeks after initiation of therapy, treatment for up to 12 weeks may be required before a beneficial effect is experienced.

Discontinue PLETAL if symptoms do not improve after 3 months.

Manufactured for OTSUKA AMERICA PHARMACEUTICAL, INC. Rockville, MD 20850 Manufactured by OTSUKA PHARMACEUTICAL CO., LTD. Tokushima 771-0182, Japan

Co-administration with food (especially high fat meal) increases the rate and also clostazol absorption

To be taken twice daily 30 minutes before or 2 hours after breakfast and evening meal