Lovastatin use in specific populations
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]
Use In Specific Populations
Pregnancy
Pregnancy Category X
Safety in pregnant women has not been established. Lovastatin immediate-release has been shown to produce skeletal malformations at plasma levels 40 times the human exposure (for mouse fetus) and 80 times the human exposure (for rat fetus) based on mg/m2 surface area (doses were 800 mg/kg/day). No drug-induced changes were seen in either species at multiples of 8 times (rat) or 4 times (mouse) based on surface area. No evidence of malformations was noted in rabbits at exposures up to 3 times the human exposure (dose of 15 mg/kg/day, highest tolerated dose of lovastatin immediate-release).
Rare reports of congenital anomalies have been received following intrauterine exposure to HMG-CoAreductase inhibitors. In a review2 of approximately 100 prospectively followed pregnancies in women exposed to lovastatin immediate-release or another structurally related HMG-CoAreductase inhibitor, the incidences of congenital anomalies, spontaneous abortions and fetal deaths/stillbirths did not exceed what would be expected in the general population. The number of cases is adequate only to exclude a 3 to 4-fold increase in congenital anomalies over the background incidence. In 89% of the prospectively followed pregnancies, drug treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. As safety in pregnant women has not been established and there is no apparent benefit to therapy with Altoprev® during pregnancy [see Contraindications (4)], treatment should be immediately discontinued as soon as pregnancy is recognized. Altoprev® should be administered to women of child-bearing potential only when such patients are highly unlikely to conceive and have been informed of the potential hazard.
Nursing Mothers
It is not known whether lovastatin is excreted in human milk. Because a small amount of another drug in this class is excreted in human breast milk and because of the potential for serious adverse reactions in nursing infants, women taking Altoprev® should not nurse their infants [see Contraindications (4)].
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Because pediatric patients are not likely to benefit from cholesterol lowering for at least a decade and because experience with this drug is limited (no studies in subjects below the age of 20 years), treatment of pediatric patients with Altoprev® is not recommended at this time.
Geriatric Use
Of the 467 patients who received Altoprev® in controlled clinical studies, 18% were 65 years and older. Of the 297 patients who received Altoprev® in uncontrolled clinical studies, 22% were 65 years and older. No overall differences in effectiveness or safety were observed between these patients and other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Thus, lower starting doses of Altoprev® are recommended for elderly patients. [see Dosage and Administration (2.2)].
Lovastatin
In pharmacokinetic studies with lovastatin immediate-release, the mean plasma level of HMG-CoAreductase inhibitory activity was shown to be approximately 45% higher in elderly patients between 70-78 years of age compared with patients between 18-30 years of age; however, clinical study experience in the elderly indicates that dosage adjustment based on this age-related pharmacokinetic difference is not needed. In the two large clinical studies conducted with lovastatin immediate-release (EXCEL and AFCAPS/TexCAPS), 21% (3094/14850) of patients were ≥65 years of age. Lipid-lowering efficacy with lovastatin was at least as great in elderly patients compared with younger patients, and there were no overall differences in safety over the 20 to 80 mg dosage range [see Clinical Pharmacology (12.3)].
Renal Impairment
In a study of patients with severe renal impairment (creatinine clearance 10–30 mL/min), the plasma concentrations of total inhibitors after a single dose of lovastatin were approximately two-fold higher than those in healthy volunteers. [see Warnings and Precautions, Skeletal Muscle Effects (5.1) and Clinical Pharmacology, Pharmacokinetics (12.3)].[1]
References
- ↑ "ALTOPREV (LOVASTATIN) TABLET, EXTENDED RELEASE [SHIONOGI INC.]". Retrieved 13 February 2014.