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Pronunciation
(fe LOE di peen)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of hypertension
Use: Unlabeled
Pediatric hypertension
Pregnancy Risk Factor
C
Pregnancy Considerations
Potentially, calcium channel blockers may prolong labor. There are no adequate or well-controlled studies in pregnant women.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Hypersensitivity to felodipine, any component of the formulation, or other calcium channel blocker
Warnings/Precautions
Concerns related to adverse effects:
• Angina/MI: Increased angina and/or MI has occurred with initiation or dosage titration of dihydropyridine calcium channel blockers; reflex tachycardia may occur resulting in angina and/or MI in patients with obstructive coronary disease especially in the absence of concurrent beta-blockade.
• Hypotension/syncope: Symptomatic hypotension with or without syncope can rarely occur; blood pressure must be lowered at a rate appropriate for the patient's clinical condition.
• Peripheral edema: The most common side effect is peripheral edema (dose dependent); occurs within 2-3 weeks of starting therapy.
Disease-related concerns:
• Aortic stenosis: Use with extreme caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia.
• Heart failure: Use with caution in patients with heart failure. Safety and efficacy have not been established.
• Hepatic impairment: Use with caution in patients with hepatic impairment; may require lower starting dose.
• Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use with caution in patients with HCM and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition.
Special populations:
• Elderly: Initiate at a lower dose in the elderly.
Other warnings/precautions:
• Titration: Dosage titration should occur after 14 days on a given dose.
Adverse Reactions
>10%: Central nervous system: Headache (11% to 15%)
2% to 10%: Cardiovascular: Peripheral edema (2% to 17%), flushing (4% to 7%), tachycardia (0.4% to 2.5%)
<1% (Limited to important or life-threatening): Abdominal pain, acid regurgitation, anemia, angioedema, angina pectoris, anxiety disorders, arm pain, arrhythmia, arthralgia, back pain, bronchitis, chest pain, CHF, constipation, contusion, CVA, decreased libido, depression, diarrhea, dizziness, dry mouth, dyspnea, dysuria, epistaxis, erythema, facial edema, flatulence, flu-like illness, flushing, foot pain, gingival hyperplasia, gynecomastia, hip pain, hypotension, impotence, influenza, insomnia, irritability, knee pain, leg pain, leukocytoclastic vasculitis, MI, muscle cramps, myalgia, nausea, nervousness, palpitation, paresthesia, pharyngitis, polyuria, premature beats, respiratory infection, sinusitis, somnolence, syncope, urinary frequency, urinary urgency, urticaria, visual disturbances, vomiting
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C8 (moderate), CYP2C9 (weak), CYP2D6 (weak), CYP3A4 (weak)
Drug Interactions
Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole systemic exposure/affects with concomitant use of a weak CYP3A4 inhibitor. Decrease aripiprazole dose to 25% of the usual dose in patients receiving both a CYP3A4 and a CYP2D6 inhibitor (regardless of potencies). Risk C: Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult product labeling for specific recommendations. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Risk C: Monitor therapy
Beta-Blockers: Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Calcium Channel Blockers (Dihydropyridine). Management: Consider calcium channel blocker (CCB) dose adjustments or alternative therapy in patients receiving concomitant carbamazepine. Nimodipine Canadian labeling contraindicates concurrent use with carbamazepine. Risk D: Consider therapy modification
Cimetidine: May increase the serum concentration of Calcium Channel Blockers. Management: Consider alternatives to cimetidine. If no suitable alternative exists, monitor for increased effects of calcium channel blockers following cimetidine initiation/dose increase, and decreased effects following cimetidine discontinuation/dose decrease. Risk D: Consider therapy modification
Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination
CycloSPORINE: May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Nicardipine may likewise inhibit the metabolism of cyclosporine. Cyclosporine dosage adjustments might be needed. Risk C: Monitor therapy
CycloSPORINE (Systemic): May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
CYP2C8 Substrates: CYP2C8 Inhibitors (Moderate) may decrease the metabolism of CYP2C8 Substrates. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Fluconazole: May decrease the metabolism of Calcium Channel Blockers. Risk C: Monitor therapy
Fosphenytoin: Calcium Channel Blockers may increase the serum concentration of Fosphenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Risk D: Consider therapy modification
Grapefruit Juice: May increase the serum concentration of Felodipine. Management: Monitor hemodynamic response to felodipine closely in patients who consume grapefruit juice. Felodipine dose adjustment and/or modification of grapefruit juice ingestion may be needed. Felodipine Canadian labeling recommends avoiding grapefruit juice. Risk D: Consider therapy modification
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Monitor for increased therapeutic effects of calcium channel blockers if an interacting macrolide antibiotic is initiated, or decreased effects if a macrolide is discontinued. Exceptions: Azithromycin; Azithromycin (Systemic); Fidaxomicin; Spiramycin. Risk D: Consider therapy modification
Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
MAO Inhibitors: May enhance the hypotensive effect of Antihypertensives. MAO Inhibitors may enhance the orthostatic hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Nafcillin: May increase the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Nitroprusside: Calcium Channel Blockers may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phenytoin: Calcium Channel Blockers may increase the serum concentration of Phenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Risk D: Consider therapy modification
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Protease Inhibitors: May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Risk D: Consider therapy modification
Rifamycin Derivatives: May increase the metabolism of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some U.S. and Canadian calcium channel blockers contraindicate use with rifampin however recommendations vary. Consult appropriate labeling. Risk D: Consider therapy modification
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tacrolimus: Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus. Risk C: Monitor therapy
Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Ethanol increases felodipine absorption. Management: Monitor for a greater hypotensive effect if ethanol is consumed.
Food: Compared to a fasted state, felodipine peak plasma concentrations are increased up to twofold when taken after a meal high in fat or carbohydrates. Grapefruit juice similarly increases felodipine Cmax by twofold. Increased therapeutic and vasodilator side effects, including severe hypotension and myocardial ischemia, may occur. Management: May be taken with a small meal that is low in fat and carbohydrates; avoid grapefruit juice during therapy.
Herb/Nutraceutical: St John's wort may decrease felodipine levels. Dong quai has estrogenic activity. Some herbal medications may worsen hypertension (eg, ephedra); garlic may have additional antihypertensive effects. Management: Avoid dong quai if using for hypertension. Avoid ephedra, yohimbe, ginseng, and garlic.
Mechanism of Action
Inhibits calcium ions from entering the “slow channels” or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization, producing a relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina
Pharmacodynamics/Kinetics
Onset of action: Antihypertensive: 2-5 hours
Duration of antihypertensive effect: 24 hours
Absorption: 100%; Absolute: 20% due to first-pass effect
Protein binding: >99%
Metabolism: Hepatic; CYP3A4 substrate (major); extensive first-pass effect
Half-life elimination: Immediate release: 11-16 hours
Excretion: Urine (70% as metabolites); feces 10%
Dosage
Oral: Hypertension:
Children (unlabeled use): Initial: 2.5 mg once daily; maximum: 10 mg/day
Adults: Oral: 2.5-10 mg once daily; usual initial dose: 5 mg; increase by 5 mg at 2-week intervals, as needed, to a maximum of 20 mg/day
Usual dose range (JNC 7) for hypertension: 2.5-20 mg once daily
Elderly: Consider lower initial doses (eg, 2.5 mg once daily) and titrate to response (Aronow, 2011)
Dosing adjustment/comments in hepatic impairment: Initial: 2.5 mg/day; monitor blood pressure
Administration: Oral
Swallow tablet whole; tablet should not be divided, crushed, or chewed. May be administered without food or with a small meal that is low in fat and carbohydrates.
Dietary Considerations
May be taken with a small meal that is low in fat and carbohydrates.
Patient Education
Take without food. Avoid concurrent alcohol (may cause dangerous hypotension). Swallow whole; do not crush or chew. May cause headache, constipation, or swelling of ankles. Report irregular heartbeat, chest pain or palpitations, persistent headache, severe constipation, peripheral swelling, weight gain, dyspnea, or respiratory changes.
Geriatric Considerations
Elderly may experience a greater hypotensive response. Constipation may be more of a problem in the elderly. Calcium channel blockers are no more effective in the elderly than other therapies; however, they do not cause significant CNS effects which is an advantage over some antihypertensive agents.
Additional Information
Felodipine maintains renal and mesenteric blood flow during hemorrhagic shock in animals.
Cardiovascular Considerations
Heart Failure: The V-HeFT III trial randomly assigned 450 male patients with chronic heart failure (on ACE Inhibitor and diuretic) to felodipine (5 mg twice daily) or placebo for an average of 18 months. After 3 month follow-up, the felodipine patients initially had an improvement in their LVEF and atrial natriuretic peptide, but those improvements did not persist. Felodipine prevented worsening of exercise tolerance and quality of life, but it was not significantly different from placebo until about 27 months into therapy. Mortality and hospitalization rates were similar between the groups. Peripheral edema occurred more frequently in the felodipine group. There is a general lack of benefit from use of felodipine in the treatment of chronic heart failure. The ACC/AHA 2009 Heart Failure Guidelines do not recommend the use of calcium channel blockers for chronic heart failure.
Hypertension: Felodipine alone or in combination with other agents is effective in the management of hypertension.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Gingival hyperplasia (fewer reports than other CCBs, resolves upon discontinuation, consultation with physician is suggested).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness; rarely may cause nervousness, insomnia, or depression
Mental Health: Effects on Psychiatric Treatment
Carbamazepine may decrease felodipine effect
Nursing: Physical Assessment/Monitoring
Use caution in presence of heart failure. When discontinuing, taper dose gradually.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, extended release, oral: 2.5 mg, 5 mg, 10 mg
Pricing: U.S. (www.drugstore.com)
Tablet, 24-hour (Felodipine)
2.5 mg (30): $42.99
5 mg (30): $49.99
10 mg (100): $192.41
References
Aronow WS, Fleg JL, Pepine CJ, et al, “ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents,” Circulation, 2011, 123(21):2434-506.
Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
Cohn JN, Ziesche S, Smith R, et al, “Effect of the Calcium Antagonist Felodipine as Supplementary Vasodilator Therapy in Patients With Chronic Heart Failure Treated With Enalapril: V-HeFT III. Vasodilator-Heart Failure Trial (V-HeFT) Study Group,” Circulation, 1997, 96(3):856-63.
Hunt SA, Abraham WT, Chin MH, et al, “2009 Focused Update Incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation,” J Am Coll Cardiol, 2009, 53(15):e1-e90.
Lindenfeld J, Albert NM, Boehmer JP, et al, “HFSA 2010 Comprehensive Heart Failure Practice Guideline,” J Card Fail, 2010, 16(6):e1-194.
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents,” Pediatrics, 2004, 114(2 Suppl):555-76.
Steele RM, Schuna AA, and Schreiber RT, “Calcium Antagonist-Induced Gingival Hyperplasia,” Ann Intern Med, 1994, 120(8):663-4.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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