Cilostazol use in specific populations: Difference between revisions
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===Renal Impairment=== | ===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%). | 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%). | ||
'''Special caution is advised when PLETAL is used in patients with severe renal impairment: estimated creatinine clearance <25 ml/min.''' | '''Special caution is advised when PLETAL is used in patients with severe renal impairment: estimated creatinine clearance <25 ml/min.''' | ||
Revision as of 21:38, 28 February 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2]
Hepatic Impairment
Patients with moderate or severe hepatic impairment have not been studied in clinical trials.
Special caution is advised when PLETAL is used in such patients.
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%). Special caution is advised when PLETAL is used in patients with severe renal impairment: estimated creatinine clearance <25 ml/min.
Pregnancy
Pregnancy Category C
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).
There are no adequate and well-controlled studies in pregnant women.
Nursing Mothers
Transfer of cilostazol into milk has been reported in experimental animals (rats). Because of the potential risk to nursing infants, a decision should be made to discontinue nursing or to discontinue PLETAL.
Pediatric Use
The safety and effectiveness of PLETAL in pediatric patients have not been established.
Geriatric Use
Of the total number of subjects (n=2274) 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 ruled out. Pharmacokinetic studies have not disclosed any age-related effects on the absorption, distribution, metabolism, and elimination of cilostazol and its metabolites.[1]
References
Adapted from the FDA Package Insert.