May 25, 2017
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Pletal

"SYDNEY, AUSTRALIA ” A small randomized trial reports sharp blood-pressure reductions in untreated hypertensives using a single pill combining four BP-lowering drugs at one-quarter the usual dose.

Among 18 patients, mean 24-hour systol"...

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Pletal




Warnings
Precautions

WARNINGS

Included as part of the "PRECAUTIONS" Section

PRECAUTIONS

Tachycardia

Cilostazol may induce tachycardia, palpitation, tachyarrhythmia or hypotension. The increase in heart rate associated with cilostazol is approximately 5 to 7 bpm. Patients with a history of ischemic heart disease may be at risk for exacerbations of angina pectoris or myocardial infarction.

Hematologic Adverse Reactions

Cases of thrombocytopenia or leukopenia progressing to agranulocytosis when PLETAL was not immediately discontinued have been reported. Agranulocytosis is reversible on discontinuation of PLETAL. Monitor platelets and white blood cell counts periodically.

Hemostatic Disorders Or Active Pathologic Bleeding

PLETAL inhibits platelet aggregation in a reversible manner. PLETAL has not been studied in patients with hemostatic disorders or active pathologic bleeding. Avoid use of PLETAL in these patients.

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.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Dietary administration of cilostazol to male and female rats and mice for up to 104 weeks, at doses up to 500 mg/kg/day in rats and 1000 mg/kg/day in mice, revealed no evidence of carcinogenic potential. The maximum doses administered in both rat and mouse studies were, on a systemic exposure basis, less than the human exposure at the MRHD of the drug. Cilostazol tested negative in bacterial gene mutation, bacterial DNA repair, mammalian cell gene mutation, and mouse in vivo bone marrow chromosomal aberration assays. It was, however, associated with a significant increase in chromosomal aberrations in the in vitro Chinese Hamster Ovary Cell assay.

Cilostazol did not affect fertility or mating performance of male and female rats at doses as high as 1000 mg/kg/day. At this dose, systemic exposures (AUCs) to unbound cilostazol were less than 1.5 times in males, and about 5 times in females, the exposure in humans at the MRHD.

Use In Specific Populations

Pregnancy

Teratogenic Effects

Pregnancy Category C.

PLETAL has been shown to be teratogenic in rats at doses that are greater than 5-times the human MRHD on a body surface area basis. There are no adequate and well-controlled studies in pregnant women.

In a rat developmental toxicity study, oral administration of 1000 mg cilostazol/kg/day was associated with decreased fetal weights, and increased incidences of cardiovascular, renal, and skeletal anomalies (ventricular septal, aortic arch and subclavian artery abnormalities, renal pelvic dilation, 14th rib, and retarded ossification). At this dose, systemic exposure to unbound cilostazol in nonpregnant rats was about 5 times the exposure in humans given the MRHD. Increased incidences of ventricular septal defect and retarded ossification were also noted at 150 mg/kg/day (5 times the MRHD on a systemic exposure basis). In a rabbit developmental toxicity study, an increased incidence of retardation of ossification of the sternum was seen at doses as low as 150 mg/kg/day. In nonpregnant rabbits given 150 mg/kg/day, exposure to unbound cilostazol was considerably lower than that seen in humans given the MRHD, and exposure to 3,4-dehydro-cilostazol was barely detectable.

When cilostazol was administered to rats during late pregnancy and lactation, an increased incidence of stillborn and decreased birth weights of offspring was seen at doses of 150 mg/kg/day (5 times the MRHD on a systemic exposure basis).

Nursing Mothers

Transfer of cilostazol into milk has been reported in rats. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from PLETAL, discontinue nursing or discontinue PLETAL.

Pediatric Use

Safety and effectiveness of PLETAL in pediatric patients have not been established.

Geriatric Use

Of the total number of subjects (n = 2,274) in clinical studies of PLETAL, 56 percent were 65 years old and over, while 16 percent were 75 years old and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be excluded. Pharmacokinetic studies have not disclosed any age-related effects on the absorption, distribution, metabolism, and elimination of cilostazol and its metabolites.

Hepatic Impairment

No dose adjustment is required in patients with mild hepatic impairment. Patients with moderate or severe hepatic impairment have not been studied in clinical trials and dosing recommendations cannot be provided [see CLINICAL PHARMACOLOGY].

Renal Impairment

No dose adjustment is required in patients with renal impairment. Patients on dialysis have not been studied, but, it is unlikely that cilostazol can be removed efficiently by dialysis because of its high protein binding (95-98%) [see CLINICAL PHARMACOLOGY].

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 9/26/2016

Warnings
Precautions

Pletal - User Reviews

Pletal User Reviews

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Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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