Felodipine

Pharmacologic Category

Antihypertensive; Calcium Channel Blocker; Calcium Channel Blocker, Dihydropyridine

Dosing: Adult

Chronic stable angina (alternative agent) (off-label use): Note: A beta-blocker is the preferred initial therapy; if there are ongoing symptoms on beta-blocker therapy, a calcium channel blocker (typically a dihydropyridine [eg, felodipine]) may be added; felodipine may be used as an alternative therapy if there are contraindications or unacceptable adverse effects with beta-blockade (ACC/AHA [Fihn 2012]).

Oral: Initial: 5 to 10 mg once daily; if initiated at 5 mg, increase dose to 10 mg once daily as tolerated after 2 to 4 weeks (Dunselman 1997; Emanuelsson 1999; Rønnevik 1995)

Hypertension: Note: For initial treatment in patients with blood pressure ≥20/10 mm Hg above goal, may be used in combination with another appropriate agent (eg, ACE inhibitor, ARB, or thiazide diuretic). For patients <20/10 mm Hg above goal, some experts recommend an initial trial of monotherapy; however, over time, many patients will require combination therapy (ACC/AHA [Whelton 2017]; Mann 2019).

Oral: Initial: 2.5 to 5 mg once daily; titrate every 1 to 2 weeks as needed based on patient response; usual dose range: 2.5 to 10 mg once daily (ACC/AHA [Whelton 2017]; Mann 2019)

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Hypertension: Oral: Consider lower initial doses (eg, 2.5 mg once daily) and titrate at no less than 2-week intervals to response (Aronow 2011).

Dosing: Renal Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

Initial: 2.5 mg once daily; monitor blood pressure closely during titration.

Dosing: Pediatric

Hypertension: Limited data available: Children ≥6 years and Adolescents: Oral: Initial: 2.5 mg once daily; may increase as needed at 2-week intervals to a maximum daily dose: 10 mg/day (AAP [Flynn 2017]; NHLBI 2011; Trachtmen 2003)

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Pediatric

There are no pediatric specific recommendations available; based on experience in adult patients, no dosage adjustments necessary; use with caution.

Dosing: Hepatic Impairment: Pediatric

There are no pediatric specific recommendations available; based on experience in adult patients, initial dosage adjustments suggested; monitor blood pressure closely during titration.

Use: Labeled Indications

Hypertension: Management of hypertension

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

​Chronic stable anginaLevel of Evidence [A, G]

Data from randomized, double-blind, placebo-controlled trials support the use of felodipine for the management of chronic stable angina, primarily in patients who continue to be symptomatic on an optimal dose of a beta-blocker Ref.

Based on the 2012 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guideline for the diagnosis and management of patients with stable ischemic heart disease, a dihydropyridine calcium channel blocker (eg, felodipine) is an effective and recommended agent in the management of chronic stable angina. A beta-blocker is the preferred initial therapy for chronic stable angina; however, a dihydropyridine calcium channel blocker (eg, felodipine) may be added if there are ongoing anginal symptoms or may be used as alternative therapy if there are contraindications or unacceptable adverse effects with beta-blockade.

Level of Evidence Definitions

​Level of Evidence Scale

Class and Related Monographs

Calcium Channel Blocking Agents

Clinical Practice Guidelines

Diabetes Mellitus:

AACE/ACE, “Consensus Statement on the Comprehensive Type 2 Diabetes Management Algorithm - 2019 Executive Summary,” January 2019

ADA, “Standards of Medical Care in Diabetes - 2020,” January 2020

Diabetes Canada, “Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada,” 2018

Heart Failure:

ACCF/AHA, “2013 ACCF/AHA Guideline for the Management of Heart Failure,” June 2013

“HFSA 2010 Comprehensive Heart Failure Practice Guideline,” July 2010

Hypertension:

"2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults," November 2017.

"ACCF/AHA Expert Consensus Document on Hypertension in the Elderly," 2011

AHA/ACC/CDC, “AHA/ACC/CDC Science Advisory: An Effective Approach to High Blood Pressure Control” November 2013

ASH/ISH “Clinical Practice Guidelines for the Management of Hypertension in the Community: A Statement by the American Society of Hypertension and the International Society of Hypertension,” January 2014

Eighth Joint National Committee (JNC 8), "2014 Evidence-based Guideline for the Management of High Blood Pressure in Adults," December 2013

Ischemic Heart Disease:

ACC/AHA/AATS/PCNA/SCAI/STS, "2014 Focused Update of the Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease," July 2014

ACCF/AHA/ACP/AATS/PCNA/SCAI/STS, “2012 Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease,” November 2012

Valvular Heart Disease:

AHA/ACC, “2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease,” March 2014

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.

Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. No IR formulation exists. Consider switching to a different dihydropyridine calcium channel blocker that is available in IR formulation.

Administration: Pediatric

Oral: Swallow tablet whole; do not divide, crush, or chew. 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.

Storage/Stability

Store below 30°C (86°F); protect from light.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat high blood pressure.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Gingival changes

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Fast heartbeat

• Severe dizziness

• Passing out

• Chest pain

• Shortness of breath

• Excessive weight gain

• Swelling of arms or legs

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Medication Safety Issues

​Sound-alike/look-alike issues:

Contraindications

Hypersensitivity to felodipine or any component of the formulation.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to other dihydropyridines; women of childbearing potential, in pregnancy, and during lactation.

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 to 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: The ACC/AHA heart failure guidelines recommend to avoid use in patients with heart failure (HF) due to lack of benefit and/or worse outcomes with calcium channel blockers in general (ACC/AHA [Yancy 2013]).

• 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.

Dosage forms specific issues:

• Lactose: May contain lactose; if necessary, consider alternative agents in patients intolerant of lactose.

* See Cautions in AHFS Essentials for additional information.

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.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in animal reproduction studies.

Chronic maternal hypertension may increase the risk of birth defects, low birth weight, preterm delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to duration and severity of maternal hypertension. Untreated hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, myocardial infarction, preeclampsia, stroke, and delivery complications (ACOG 203 2019).

Calcium channel blockers may be used to treat hypertension in pregnant women; however, agents other than felodipine are more commonly used (ACOG 203 2019; ESC [Regitz-Zagrosek 2018]). Females with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]).

Breast-Feeding Considerations

It is not known if felodipine is present in breast milk.

Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother.

Briggs' Drugs in Pregnancy & Lactation

• Felodipine

Adverse Reactions

>10%:

Cardiovascular: Peripheral edema (2% to 17%)

Central nervous system: Headache (11% to 15%)

1% to 10%: Cardiovascular: Flushing (4% to 7%), tachycardia (≤3%)

<1%, postmarketing, and/or case reports: Abdominal pain, acid regurgitation, anemia, angina pectoris, angioedema, anxiety disorder, arm pain, arthralgia, back pain, bronchitis, bruise, cardiac arrhythmia, cardiac failure, cerebrovascular accident, chest pain, constipation, decreased libido, depression, diarrhea, dizziness, drowsiness, dyspnea, dysuria, epistaxis, erythema, extrasystoles, facial edema, flatulence, flu-like symptoms, flushing, foot pain, gingival hyperplasia, gynecomastia, hip pain, hypersensitivity angiitis, hypotension, impotence, influenza, insomnia, irritability, knee pain, leg pain, muscle cramps, myalgia, myocardial infarction, nausea, nervousness, palpitations, paresthesia, pharyngitis, polyuria, respiratory tract infection, sinusitis, syncope, urinary frequency, urinary urgency, urticaria, visual disturbance, vomiting, xerostomia

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Calcium Channel Blocker, Dihydropyridine Allergy

Toxicology

• Calcium Channel Blockers

Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (weak)

Drug Interactions Open Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Risk D: Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May enhance the adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Fluconazole and isavuconazonium likely exert weaker effects than other azoles and are addressed in separate monographs. Management: Concurrent use of felodipine or nisoldipine with itraconazole is specifically contraindicated. Frequent monitoring is warranted with any such combination; calcium channel blocker dose reductions may be required. Exceptions: Fluconazole; Isavuconazonium Sulfate. Risk D: Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. 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

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bitter Orange: May increase the serum concentration of Felodipine. Risk C: Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

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

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

CycloSPORINE (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination. Some combinations are specifically contraindicated by manufacturers; others may have recommended dose adjustments. If combined, monitor for increased substrate effects. Risk D: Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Efavirenz: May decrease the serum concentration of Calcium Channel Blockers. Risk C: Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fluconazole: May increase the serum concentration of Calcium Channel Blockers. Risk C: Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fosphenytoin: Calcium Channel Blockers may increase the serum concentration of Fosphenytoin. Calcium Channel Blockers may decrease 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

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Grapefruit Juice: May increase the serum concentration of Felodipine. Risk C: Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Itraconazole: May increase the serum concentration of Felodipine. Risk X: Avoid combination

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Ketoconazole (Systemic): May increase the serum concentration of Felodipine. Risk X: Avoid combination

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; 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

Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Risk D: Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Risk D: Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Phenytoin: Calcium Channel Blockers may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers. Management: Avoid use of nimodipine or nifedipine with phenytoin. Monitor for phenytoin toxicity and/or decreased calcium channel blocker effects with any concurrent use. Risk D: Consider therapy modification

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Rifamycin Derivatives: May decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some US and Canadian calcium channel blockers contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling. Risk D: Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Risk D: Consider therapy modification

Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Talazoparib: Felodipine may increase the serum concentration of Talazoparib. Risk C: Monitor therapy

Thioridazine: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Thioridazine. Management: Consider avoiding concomitant use of thioridazine and weak CYP2D6 inhibitors. If combined, monitor closely for QTc interval prolongation and arrhythmias. Some weak CYP2D6 inhibitors list use with thioridazine as a contraindication. Risk D: Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Food Interactions

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. Monitor hemodynamic response closely in patients consuming grapefruit juice concurrently; felodipine dosage adjustment and/or modification of grapefruit juice ingestion may be needed.

Test Interactions

May lead to false-negative aldosterone/renin ratio (ARR) (Funder 2016).

Genes of Interest

• Cytochrome P450 3A4
• P-Glycoprotein

Monitoring Parameters

BP, heart rate

Hypertension: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2017]):

Confirmed hypertension and known CVD or 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10%: Target BP <130/80 mm Hg is recommended.

Confirmed hypertension without markers of increased ASCVD risk: Target BP <130/80 mm Hg may be reasonable.

Diabetes and hypertension: The American Diabetes Association (ADA) guidelines (ADA 2020):

Patients 18 to 65 years of age, without ASCVD, and 10-year ASCVD risk <15%: Target BP <140/90 mm Hg is recommended.

Patients 18 to 65 years of age and known ASCVD or 10-year ASCVD risk ≥15%: Target BP <130/80 mm Hg may be appropriate if it can be safely attained.

Patients >65 years of age (healthy or complex/intermediate health): Target BP <140/90 mm Hg is recommended.

Patients >65 years of age (very complex/poor health): Target BP <150/90 mm Hg is recommended.

Advanced Practitioners Physical Assessment/Monitoring

Obtain liver function tests; dosage adjustments may be needed. Screen patient for a history of heart failure, hypertrophic cardiomyopathy, or hepatic impairment. Assess for signs and symptoms of developing heart failure. Assess other medications patient may be taking; alternate therapy or dosage adjustments may be needed. Assess for signs of dizziness.

Nursing Physical Assessment/Monitoring

Check ordered labs and report any abnormalities. Monitor patient’s cardiovascular status including blood pressure, heart rate, rhythm, ECG changes, and signs of new heart failure (peripheral edema, pulmonary congestion, weight gain, increased shortness-of-breath). Teach patients orthostatic precautions (rise slowly, call for assistance, notify nurse if feeling dizzy or faint). Educate patients that peripheral edema may occur within 2 to 3 weeks of starting this medicine. Educate patients that drinking alcohol while taking this medicine may cause severe hypotensive side effects. Instruct patient to take with a low fat and low carbohydrate meal and to limit grapefruit juice.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Extended Release 24 Hour, Oral:

Generic: 2.5 mg, 5 mg, 10 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Extended Release 24 Hour, Oral:

Plendil: 2.5 mg, 5 mg, 10 mg

Generic: 2.5 mg, 5 mg, 10 mg

Anatomic Therapeutic Chemical (ATC) Classification

• C08CA02

Generic Available (US)

Yes

Pricing: US

Tablet, 24-hour (Felodipine ER Oral)

2.5 mg (per each): $1.22 - $1.58

5 mg (per each): $1.08 - $1.58

10 mg (per each): $2.18 - $3.72

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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 to 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 to 16 hours

Time to peak: 2.5 to 5 hours

Excretion: Urine (70% as metabolites); feces 10%

Pharmacodynamics/Kinetics: Additional Considerations

Hepatic function impairment: Felodipine clearance is reduced about 60% in patients with hepatic impairment.

Geriatric: Plasma concentrations of felodipine increase with advancing age. Clearance of felodipine in elderly hypertensive patients was 45% of that observed in young volunteers. Steady-state mean area under curve in young patients was 39% of that observed in elderly patients.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

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).

Effects on Bleeding

No information available to require special precautions

Related Information

• Calcium Channel Blockers − Comparative Pharmacokinetics
• Oral Medications That Should Not Be Crushed or Altered

Index Terms

Plendil

FDA Approval Date

August 01, 1991

References

American College of Obstetricians and Gynecologists (ACOG). ACOG Committee Opinion No. 743: Low-dose aspirin use during pregnancy. Obstet Gynecol. 2018;132(1):e44-e52. doi: 10.1097/AOG.0000000000002708.[PubMed 29939940]

American College of Obstetricians and Gynecologists (ACOG). ACOG practice bulletin no. 203: chronic hypertension in pregnancy. Obstet Gynecol. 2019;133(1):e26-e50.[PubMed 30575676]

American Diabetes Association (ADA). Standards of medical care in diabetes–2020. Diabetes Care. 2020;43(suppl 1):S1-S212. https://care.diabetesjournals.org/content/43/Supplement_1. Accessed January 22, 2020.

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):2434-2506.[PubMed 21518977]

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):2560-2571.

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):856-863.[PubMed 9264493]

Dunselman P, Liem AH, Verdel G, Kragten H, Bosma A, Bernink P. Addition of felodipine to metoprolol vs replacement of metoprolol by felodipine in patients with angina pectoris despite adequate beta-blockade. Results of the Felodipine ER and Metoprolol CR in Angina (FEMINA) Study. Working Group on Cardiovascular Research, The Netherlands (WCN). Eur Heart J. 1997;18(11):1755-1764.[PubMed 9402450]

Emanuelsson H, Egstrup K, Nikus K, et al. Antianginal efficacy of the combination of felodipine-metoprolol 10/100 mg compared with each drug alone in patients with stable effort-induced angina pectoris: a multicenter parallel group study. The TRAFFIC Study Group. Am Heart J. 1999;137(5):854-862.[PubMed 10220634]

Felodipine [prescribing information]. Las Vegas, NV: Yiling Pharmaceutical Inc; July 2018.

Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012;126(25):3097-3137.[PubMed 23166211]

Flynn JT, Kaelber DC, Baker-Smith CM, et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017;140(3).[PubMed 28827377]

Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi: 10.1210/jc.2015-4061.[PubMed 26934393]

Go AS, Bauman M, King SM, et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention [published online November 15, 2013]. Hypertension.[PubMed 24243703]

James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520.[PubMed 24352797]

Lombardi T, Fiore-Donno G, Belser U, et al. Felodipine-Induced Gingival Hyperplasia: A Clinical and Histologic Study. J Oral Pathol Med. 1991;20(2):89-92.

Mann JFE. Choice of drug therapy in primary (essential) hypertension. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 21, 2019.

Moncica I, Oh PI, ul Qamar I, et al. A crossover comparison of extended release felodipine with prolonged action nifedipine in hypertension. Arch Dis Child. 1995;73(2):154-156.[PubMed 28827377]

National Heart, Lung, and Blood Institute. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. Clinical Practice Guidelines, 2011, National Institutes of Health. http://www.nhlbi.nih.gov/guidelines/cvd_ped/peds_guidelines_full.pdf.

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):555-576.[PubMed 15286277]

Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(23):2440-2492. doi: 10.1161/CIR.0000000000000029.[PubMed 24589852]

Plendil (felodipine) [prescribing information]. Wilmington, DE: AstraZeneca LP; October 2012.

Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J. 2018;39(34):3165-3241.[PubMed 30165544]

Rønnevik PK, Silke B, Ostergaard O. Felodipine in addition to beta-adrenergic blockade for angina pectoris. a multicentre, randomized, placebo-controlled trial. Eur Heart J. 1995;16(11):1535-1541.[PubMed 8881845]

Steele RM, Schuna AA, Schreiber RT. Calcium Antagonist-Induced Gingival Hyperplasia. Ann Intern Med. 1994;120(8):663-664.[PubMed 8135450]

Trachtman H, Frank R, Mahan JD, et al. Clinical trial of extended-release felodipine in pediatric essential hypertension. Pediatr Nephrol. 2003;18(6):548-553.[PubMed 12700955]

Weber MA, Schiffrin EL, White WB, et al, Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014;16(1):14-26.[PubMed 24341872]

Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published online ahead of print on November 13, 2017.]. Hypertension. doi: 10.1161/HYP.0000000000000065.[PubMed 29133356]

Yancy CW, Jessup M, Bozkurt B, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128(16):e240-e327.[PubMed 23741058]

Young PC, Turiansky GW, Sau P, et al. Felodipine-Induced Gingival Hyperplasia. Cutis. 1998;62(1):41-43.[PubMed 9675532 ]

Brand Names: International

AGON SR (NZ); Dilahex (PH); Dilofen ER (PH); Dilopin (KR); Fedil (TW); Fedil SR (TH); Felo ER (NZ, TW); Feloblock (EG); Felocor (DE); Felocor Retardtab (DE); Felodil ER (VN); Felodil XR (AU); Felodip (UA); Felodur ER (AU); Felogamma Retard (DE); Felogard (IN); Felogard-ER (LK); Felopine 5 (TH); Felopine-SR (TW); Felostad 5 Retard (HK); Feloten (TH); Felpin (TW); Felpin E.R. (PH); Feltor (ZW); Flodil LP (FR); Hidipine (KR); Hydac (FI, SE); Keliping (CN); Keydipin ER (KR); Lodil (KR); Lodipin ER (KR); Lodistad MR (PH); Mibeplen (VN); Modip (DE); Munobal (DE, KR, MX, VE); Munobal Retard (AT, DE); Nirmadil (ID); Penedil (IL); Perfudal (ES); Phenodical (CR, DO, GT, HN, NI, PA, SV); Plendil (AE, AR, BB, BE, BF, BG, BH, BJ, BM, BS, BZ, CH, CI, CN, CR, CU, CY, CZ, DK, DO, EE, EG, ES, ET, FI, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, HU, IE, IN, IQ, IR, IS, IT, JM, JO, KE, KW, LB, LK, LR, LT, LU, LV, LY, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NI, NL, OM, PA, PE, PK, PL, PR, PY, QA, RO, RU, SA, SC, SD, SE, SK, SL, SN, SR, SV, SY, TH, TN, TT, TW, TZ, UG, VN, YE, ZA, ZM); Plendil Depottab (NO); Plendil ER (AU, NZ, PH); Plendil PR (TR); Plendil Retard (AT); Plentopine (EG); Polo (TW); Presid (LV); Preslow (PT); Renedil (LU); Splendil (BR, CL, JP); Splendil ER (KR); Stapin ER (KR); Topidil (TH); Vascalpha (GB); Vaspine ER (KR); Versant XR (PH)

Last Updated 10/9/20