CILOSTAZOL tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

CILOSTAZOL (UNII: N7Z035406B) (CILOSTAZOL - UNII:N7Z035406B)

Available from:

AvPAK

INN (International Name):

CILOSTAZOL

Composition:

CILOSTAZOL 50 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Cilostazol tablets are indicated for the reduction of symptoms of intermittent claudication, as demonstrated by an increased walking distance. Cilostazol is contraindicated in patients with: - Heart failure of any severity: Cilostazol and several of its metabolites are inhibitors of phosphodiesterase III. Several drugs with this pharmacologic effect have caused decreased survival compared to placebo in patients with class III-IV heart failure. - Hypersensitivity to cilostazol or any components of cilostazol tablets (e.g., anaphylaxis, angioedema) Teratogenic Effects Pregnancy Category C. Cilostazol 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, 14 th   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). 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 cilostazol, discontinue nursing or discontinue cilostazol. Safety and effectiveness of cilostazol in pediatric patients have not been established. Of the total number of subjects (n = 2,274) in clinical studies of cilostazol, 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. 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 ( 12.3)]. 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 to 98%) [see Clinical Pharmacology ( 12.3)].

Product summary:

Cilostazol tablets, USP are supplied as 50 mg and 100 mg tablets. Cilostazol tablets, USP 50 mg are white, round, flat-faced, bevelled-edge tablets, engraved "APO" on one side and "CIL" over "50" on the other side. They are supplied as follows: NDC 50268-176-15 (10 tablets per card, 5 cards per carton). Cilostazol tablets, USP 100 mg tablets are white, round, flat-faced, bevelled-edge tablets, engraved "APO" on one side and "CIL" over "100" on the other side. They are supplied as follows: NDC 50268-177-15 (10 tablets per card, 5 cards per carton). Store cilostazol tablets at 25°C (77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

CILOSTAZOL- CILOSTAZOL TABLET
AVPAK
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HIGHLIGHTS OF PRESCRIBING INFORMATION
CILOSTAZOL TABLETS, USP
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
CILOSTAZOL TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
CILOSTAZOL TABLETS.
CILOSTAZOL TABLETS, FOR ORAL USE.
INITIAL U.S. APPROVAL: 1999
WARNING: CONTRAINDICATED IN HEART FAILURE PATIENTS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
CILOSTAZOL TABLETS IS CONTRAINDICATED IN PATIENTS WITH HEART FAILURE
OF ANY SEVERITY.
CILOSTAZOL AND SEVERAL OF ITS METABOLITES ARE INHIBITORS OF
PHOSPHODIESTERASE III.
SEVERAL DRUGS WITH THE PHARMACOLOGIC EFFECT HAVE CAUSED DECREASED
SURVIVAL
COMPARED TO PLACEBO PATIENTS WITH CLASS III-IV HEART FAILURE. (4)
RECENT MAJOR CHANGES
Warnings and Precautions, Left Ventricular Outflow Obstruction (5.2)
05/2017
INDICATIONS AND USAGE
Cilostazol is a phosphodiesterase III inhibitor (PDE III inhibitor)
indicated for the reduction of symptoms of
intermittent claudication, as demonstrated by an increased walking
distance ( 1)
DOSAGE AND ADMINISTRATION
The recommended dosage of cilostazol is 100 mg twice daily taken at
least half an hour before or two
hours after breakfast and dinner ( 2.1)
Reduce the dose to 50 mg twice daily when coadministered with CYP3A4
inhibitors such as
ketoconazole, itraconazole, erythromycin, and diltiazem, or CYP2C19
inhibitors such as ticlopidine,
fluconazole, and omeprazole ( 2.2)
DOSAGE FORMS AND STRENGTHS
Tablets: 50 mg and 100 mg ( 3)
CONTRAINDICATIONS
Heart failure of any severity ( 4)
Hypersensitivity to cilostazol or any components of cilostazol tablets
( 4)
WARNINGS AND PRECAUTIONS
Risks of tachycardia, palpitation, tachyarrhythmia or hypotension.
Risks of exacerbations of angina
pectoris or myocardial infarction in patients with a history of
ischemic heart disease ( 5.1)
Left ventricular outflow tract obstruction has been reported in
patients with sigmoid shaped
interventricular septum ( 5.2)
Risks of thrombocytopenia or leukopenia progressing to