Felodipine precautions

List of precautions
General Carcinogenesis Mutagenesis Impairment of fertility Pregnancy Nursing mothers Pediatric use Geriatric use
 * Hypotension
 * Heart failure
 * Patients with impaired liver function
 * Peripheral edema
 * Teratogenic effects
 * Nonteratogenic effects

Hypotension
Felodipine, like other calcium antagonists, may occasionally precipitate significant hypotension and, rarely, syncope. It may lead to reflex tachycardia which in susceptible individuals may precipitate angina pectoris. Return to top

Heart failure
Although acute hemodynamic studies in a small number of patients with NYHA Class II or III heart failure treated with Felodipine have not demonstrated negative inotropic effects, safety in patients with heart failure has not been established. Caution, therefore, should be exercised when using Felodipine in patients with heart failure or compromised ventricular function, particularly in combination with a beta blocker. Return to top

Patients with impaired liver function
Patients with impaired liver function may have elevated plasma concentrations of Felodipine and may respond to lower doses of Felodipine; therefore, a starting dose of 2.5 mg once a day is recommended. These patients should have their blood pressure monitored closely during dosage adjustment of Felodipine. Return to top

Peripheral edema
Peripheral edema, generally mild and not associated with generalized fluid retention, was the most common adverse event in the clinical trials. The incidence of peripheral edema was both dose and age dependent. Frequency of peripheral edema ranged from about 10% in patients under 50 years of age taking 5 mg daily to about 30% in those over 60 years of age taking 20 mg daily. This adverse effect generally occurs within 2-3 weeks of the initiation of treatment. Return to top

Carcinogenesis
In a 2-year carcinogenicity study in rats fed Felodipine at doses of 7.7, 23.1 or 69.3 mg/kg/day (up to 61 times1 the maximum recommended human dose on a mg/m2 basis), a dose-related increase in the incidence of benign interstitial cell tumors of the testes (Leydig cell tumors) was observed in treated male rats. These tumors were not observed in a similar study in mice at doses up to 138.6 mg/kg/day (61 times1 the maximum recommended human dose on a mg/m2 basis). Felodipine, at the doses employed in the 2-year rat study, has been shown to lower testicular testosterone and to produce a corresponding increase in serum luteinizing hormone in rats. The Leydig cell tumor development is possibly secondary to these hormonal effects which have not been observed in man. Felodipine was not carcinogenic when fed to mice at doses up to 138.6 mg/kg/day (61 times1 the maximum recommended human dose on a mg/m2 basis) for periods of up to 80 weeks in males and 99 weeks in females. Return to top

Mutagenesis
Felodipine did not display any mutagenic activity in vitro in the Ames microbial mutagenicity test or in the mouse lymphoma forward mutation assay. No clastogenic potential was seen in vivo in the mouse micronucleus test at oral doses up to 2500 mg/kg (1,100 times1 the maximum recommended human dose on a mg/m2 basis) or in vitro in a human lymphocyte chromosome aberration assay. Return to top

Impairment of fertility
A fertility study in which male and female rats were administered doses of 3.8, 9.6 or 26.9 mg/kg/day (up to 24 times1 the maximum recommended human dose on a mg/m2 basis) showed no significant effect of Felodipine on reproductive performance. Return to top

Pregnancy

 * Pregnancy category C. Return to top

Teratogenic effects
Studies in pregnant rabbits administered doses of 0.46, 1.2, 2.3, and 4.6 mg/kg/day (from 0.8 to 8 times1 the maximum recommended human dose on a mg/m2 basis) showed digital anomalies consisting of reduction in size and degree of ossification of the terminal phalanges in the fetuses. The frequency and severity of the changes appeared dose related and were noted even at the lowest dose. These changes have been shown to occur with other members of the dihydropyridine class and are possibly a result of compromised uterine blood flow. Similar fetal anomalies were not observed in rats given Felodipine. In a teratology study in cynomolgus monkeys, no reduction in the size of the terminal phalanges was observed, but an abnormal position of the distal phalanges was noted in about 40% of the fetuses. Return to top

Nonteratogenic effects
A prolongation of parturition with difficult labor and an increased frequency of fetal and early postnatal deaths were observed in rats administered doses of 9.6 mg/kg/day (8 times1 the maximum human dose on a mg/m2 basis) and above. Significant enlargement of the mammary glands, in excess of the normal enlargement for pregnant rabbits, was found with doses greater than or equal to 1.2 mg/kg/day (2.1 times the maximum human dose on a mg/m2 basis). This effect occurred only in pregnant rabbits and regressed during lactation. Similar changes in the mammary glands were not observed in rats or monkeys. There are no adequate and well-controlled studies in pregnant women. If Felodipine is used during pregnancy, or if the patient becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus, possible digital anomalies of the infant, and the potential effects of Felodipine on labor and delivery and on the mammary glands of pregnant females. Return to top

Nursing mothers
It is not known whether this drug is secreted in human milk and because of the potential for serious adverse reactions from Felodipine in the infant, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Return to top

Pediatric use
Safety and effectiveness in pediatric patients have not been established. Return to top

Geriatric use
Clinical studies of Felodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Pharmacokinetics, however, indicate that the availability of Felodipine is increased in older patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Return to top