VA Class:CV200
Felodipine is a 1,4-dihydropyridine-derivative calcium-channel blocking agent (calcium-channel blocker).1, 2
Felodipine is used alone or in combination with other classes of antihypertensive agents in the management of hypertension.1, 2, 3, 1200
Calcium-channel blockers (e.g., felodipine) are considered one of several preferred antihypertensive drug classes for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, and thiazide diuretics.501, 502, 503, 504, 1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501, 502, 504, 1200, 1213 (See Uses: Hypertension, in Amlodipine 24:28.08.)
Calcium-channel blockers may be beneficial in the management of hypertension in patients with certain coexisting conditions such as ischemic heart disease (e.g., angina)523 and in geriatric patients, including those with isolated systolic hypertension.502, 510 (See Uses: Hypertension, in Amlodipine 24:28.08.)
In the Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study, the long-term cardiovascular morbidity and mortality benefit of a long-acting dihydropyridine calcium-channel blocker (amlodipine), a thiazide-like diuretic (chlorthalidone), and an ACE inhibitor (lisinopril) were compared in a broad population of patients with hypertension at risk for coronary heart disease.75, 76, 81, 82, 83, 84 Although these antihypertensive agents were comparably effective in providing important cardiovascular benefit, apparent differences in certain secondary outcomes were observed.75, 76 Patients receiving the ACE inhibitor experienced higher risks of stroke, combined cardiovascular disease, GI bleeding, and angioedema, while those receiving the calcium-channel blocker were at higher risk of developing heart failure.83, 84 The ALLHAT investigators suggested that the favorable cardiovascular outcome may be attributable, at least in part, to the greater antihypertensive effect of the calcium-channel blocker compared with that of the ACE inhibitor, especially in women and black patients.83, 84 (See Clinical Benefits of Thiazides in Hypertension under Hypertension in Adults: Treatment Benefits, in Uses in the Thiazides General Statement 40:28.20.)
Most patients with hypertension, especially black patients, will require at least 2 antihypertensive drugs to achieve adequate blood pressure control.1200 Calcium-channel blockers may be particularly useful in the management of hypertension in black patients;81, 82, 501, 504, 1250, 1251, 1252, 1253, 1254, 1255 these patients tend to have greater blood pressure response to calcium-channel blockers and thiazide diuretics than to other antihypertensive drug classes (e.g., ACE inhibitors, angiotensin II receptor antagonists).501, 504, 1200 However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar blood pressure lowering in black patients as in other racial groups.1200 (See Race under Hypertension: Other Special Considerations for Antihypertensive Therapy, in Uses in Amlodipine 24:28.08.)
For additional information on the role of calcium-channel blockers in the management of hypertension, see Uses: Hypertension, in Amlodipine 24:28.08. For information on overall principles and expert recommendations for treatment of hypertension, see Uses: Hypertension in Adults and also see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
Because of the slow onset of hypotensive effect with extended-release tablets containing felodipine,1, 2, 3 these dosage forms are not suitable for use as acute therapy in rapidly reducing blood pressure in patients with severe hypertension in whom reduction of blood pressure is considered urgent (i.e., hypertensive urgencies) nor in hypertensive emergencies.7
Felodipine is administered orally as extended-release tablets.1, 2, 3 The tablets should be swallowed intact and should not be chewed or crushed.1 Since peak concentrations of the drug were increased by 60% when felodipine was administered with a high-fat or high-carbohydrate meal and no changes in pharmacokinetics were observed when the drug was administered with a light meal (e.g., orange juice, toast, and cereal), the manufacturer states that felodipine should be taken either without food or with a light meal.1 However, the bioavailability of felodipine as determined by area under the plasma concentration-time curve (AUC) was not affected when the extended-release tablets containing felodipine were administered with a high-fat or high-carbohydrate meal.1
Concomitant administration with doubly concentrated grapefruit juice has been shown to increase oral bioavailability of felodipine twofold compared with concomitant administration with orange juice or water.1, 8, 53, 67, 69 Concomitant oral administration of 1,4-dihydropyridine-derivative calcium-channel blocking agents (e.g., felodipine) with grapefruit juice usually should be avoided since potentially clinically important increases in hemodynamic effects can result.45, 64, 65, 66, 69 (See Drug Interactions: Grapefruit Juice, in Nifedipine 24:28.08.)
In addition, important drug interactions may occur when felodipine is administered concomitantly with some other drugs.1, 51 Metabolism of felodipine is mediated by the cytochrome P-450 (CYP) isoenzyme 3A4 and the possibility exists that drugs and foods that inhibit this isoenzyme (e.g., ketoconazole, itraconazole, erythromycin, grapefruit juice, cimetidine) may increase plasma felodipine concentrations several-fold, which may result in increased cardiac effects (e.g., decreases in blood pressure and increases in heart rate).1, 51 Therefore, the manufacturer states that caution should be exercised in the concomitant use of felodipine and these known inhibitors of the CYP enzyme system.1, 51 The possibility that felodipine may share the drug interaction potential of nifedipine, another 1,4-dihydropyridine derivative, also should be considered and the usual precautions observed. (See Drug Interactions in Nifedipine 24:28.08.)
For the management of hypertension in adults, the initial dosage of felodipine is 2.5-5 mg once daily.1 Dosage of the drug should be adjusted according to the patient's blood pressure response and tolerance, generally at intervals of not less than 2 weeks.1 The usual maintenance dosage in adults is 2.5-10 mg once daily.1, 1200 While dosages exceeding 10 mg daily were associated with an increased blood pressure response in clinical studies, such dosages were also associated with exaggerated adverse vasodilatory effects (e.g, peripheral edema).1
Although safety and efficacy remain to be fully established in children, 1, 51 some experts have recommended pediatric dosages for hypertension based on clinical experience. 1150 If felodipine is used for the management of hypertension in children†, a usual initial dosage of 2.5 mg once daily is recommended in children at least 6 years of age.1150 Experts state that the dosage may be increased every 2-4 weeks until blood pressure is controlled, the maximum dosage is reached (10 mg once daily), or adverse effects occur.1150 For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
Blood Pressure Monitoring and Treatment Goals
Blood pressure should be monitored regularly (i.e., monthly) during therapy and dosage of the antihypertensive drug adjusted until blood pressure is controlled.1200 If an adequate blood pressure response is not achieved with calcium-channel blocker monotherapy, the dosage may be increased or another antihypertensive agent with demonstrated benefit and preferably with a complementary mechanism of action (e.g., angiotensin-converting enzyme [ACE] inhibitor, angiotensin II receptor antagonist, thiazide diuretic) may be added; if target blood pressure is still not achieved, a third drug may be added.1200, 1216 (See Uses: Hypertension.) In patients who develop unacceptable adverse effects with felodipine, the drug should be discontinued and another antihypertensive agent from a different pharmacologic class should be initiated.1200, 1216
The goal of hypertension management and prevention is to achieve and maintain optimal control of blood pressure.1200 However, the optimum blood pressure threshold for initiating antihypertensive drug therapy and specific treatment goals remain controversial.505, 506, 507, 508, 515, 523, 530, 1201, 1207, 1209, 1222 A 2017 multidisciplinary hypertension guideline from the American College of Cardiology (ACC), American Heart Association (AHA), and a number of other professional organizations generally recommends a blood pressure goal of less than 130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200, 1207 Many patients will require at least 2 drugs from different pharmacologic classes to achieve this blood pressure goal; the potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs also should be considered when deciding a patient's blood pressure treatment goal.1200, 1220
Dosage in Hepatic or Renal Impairment and in Geriatric Patients
Dosage of felodipine should be adjusted carefully and blood pressure response should be closely monitored with each dosage adjustment in geriatric patients and in patients with impaired hepatic function; the usual initial dosage is 2.5 mg daily in such patients.1, 68 In clinical trials, the risk of peripheral edema was increased substantially in geriatric patients receiving dosages exceeding 10 mg daily.1 Adjustment of felodipine dosage generally is not necessary in patients with renal impairment.1
Felodipine is a 1,4-dihydropyridine-derivative calcium-channel blocking agent that is structurally related to nifedipine and nimodipine.1, 2
Additional Information
SumMon® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the labeling be consulted for detailed information on the usual cautions, precautions, and contraindications.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, extended-release | 2.5 mg* | Felodipine Extended-release Tablets | |
5 mg* | Felodipine Extended-release Tablets | |||
Plendil® | AstraZeneca | |||
10 mg* | Felodipine Extended-release Tablets | |||
Plendil® | AstraZeneca |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
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