Earn CME/CE in your profession:

Continuing Education Activity

Felodipine is a medication used in the management and treatment of essential hypertension. It is a member of the dihydropyridine class of calcium channel blockers. Reduction in blood pressure lowers the risk of cardiovascular morbidity and mortality. The most significant benefit of the antihypertensive effect of felodipine is a decrease in the incidence of stroke. This activity describes felodipine's indications, action, and contraindications as a valuable agent in treating essential hypertension. In addition, this activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for interprofessional team members in the treatment of patients with essential hypertension.


  • Identify the mechanism of action of felodipine.
  • Describe the adverse effects of felodipine.
  • Summarize the monitoring for toxicity of felodipine.
  • Explain interprofessional team strategies for improving care coordination and educating the patients regarding compliance with felodipine.


Felodipine is an agent in the dihydropyridine class of calcium channel blockers. Felodipine is FDA approved and indicated in the treatment of essential hypertension. Reduction in blood pressure lowers the risk of cardiovascular morbidity and mortality. The most significant benefit of the antihypertensive effect of felodipine is a decrease in the incidence of stroke. In patients presenting with mild to moderate hypertension, felodipine ER monotherapy is equivalent in efficacy to cardio-selective beta-blockers, thiazide diuretics, ACE inhibitors, and other calcium channel antagonists. In patients with severe hypertension uncontrolled by beta-blockers and diuretics, felodipine ER can be an add-on therapy.[1][2][3]

Non-FDA approved uses of felodipine:

  • Renovascular hypertension
  • Pulmonary hypertension
  • Chronic stable angina pectoris[4]
  • Congestive heart failure[5]
  • Prevention of the decline in renal function caused by calcineurin inhibitors in lung transplantation patients[6]
  • In preclinical studies,  felodipine shows promising results in bleomycin-induced pulmonary fibrosis. However, research is needed before using felodipine to prevent bleomycin-induced pulmonary fibrosis in humans.[7]

Mechanism of Action

The first step in vascular smooth muscle contraction is the influx of calcium into the smooth muscle cell via voltage-dependent L-type calcium channels. Cytosolic calcium binding to calmodulin follows this action, resulting in the activation of myosin light-chain kinase (MLCK). The activated MLCK phosphorylates the myosin light chain resulting in the attachment of the myosin head with actin, ultimately causing smooth-muscle contraction and vasoconstriction. The vascular smooth muscle contraction causes an increase in peripheral vascular resistance and an increase in blood pressure.[8] 

Like the other dihydropyridine calcium-channel blockers, felodipine blocks the voltage-dependent L-type calcium channels and prevents calcium entry into the smooth muscle cell. Reduced cytosolic calcium decreases peripheral vascular resistance, resulting in vasodilation and a decrease in blood pressure. Felodipine selectively dilates arterioles and has no impact on venous vessels. In the in-vitro studies, research shows that felodipine has a higher selectivity than other commonly used dihydropyridine calcium channel blockers like amlodipine and nifedipine for vascular tissue in comparison to cardiac tissue. Also, the clinical trials of felodipine have not shown any negative inotropic effect.[9]

Felodipine results in a dose-dependent decrease in systolic and diastolic blood pressure. Additionally, felodipine causes a reflex increase in heart rate (reflex tachycardia).


Absorption: Felodipine is almost completely absorbed after oral administration. However, the bioavailability is only about 20% because of the extensive first-pass metabolism of felodipine—the plasma concentration of felodipine increases when administered along with high fat or high carbohydrate diet. Additionally, grapefruit juice administration increases the plasma concentration of felodipine.[10]

Distribution: Felodipine is highly protein-bound and has a high volume of distribution(about 10 L/kg). Felodipine administration with alcohol results in a significant increase in the absorption of felodipine. Peak plasma concentration(Cmax) increased by almost 150%, and time to peak plasma concentration(Tmax) decreased by one h after intake of alcohol in simulation. Concurrent administration of alcohol with felodipine should be generally avoided.[11]

Metabolism: Felodipine is metabolized in the liver and weakly inhibits CYP3A4 and CYP2D6 enzymes.[12][13]

Excretion: Approximately 70 % of felodipine is excreted as metabolites in the urine; biliary secretion is a minor route of eliminating felodipine, with 10 %  of the administered dose recovered in the feces.[14][15]


Felodipine is an orally administered drug. It is available in the strengths of 2.5 mg, 5 mg, and 10 mg. Felodipine dosing is often an extended-release (ER) tablet formulation. The ER formulation offers several benefits, including once-daily dosing, minimal drug interactions, and lesser adverse effects. Therefore, starting the patient on a 5 mg dose of felodipine ER once daily is recommended. If the dose needs to be adjusted, a decrease or increase of 2.5 mg should be done every two weeks. The recommended dosage range of felodipine is 2.5 to 10 mg once daily. The tablet should be swallowed whole and not crushed or chewed. It can be taken with or without food or with a light meal.

Use in Specific Patient Populations

Patients with Hepatic Impairment: It is not recommended to use felodipine in patients with hepatic impairment. Patients with liver impairment have higher plasma concentrations of felodipine since it undergoes hepatic metabolism and, if needed, are started at 2.5 mg once daily dosing. These patients need to have their blood pressure monitored closely during dose adjustment.[16][14]

Patients with Renal Impairment: Felodipine is safe for use in patients with renal failure.[17]

Pregnancy Considerations: In animal studies, felodipine has been shown to cause teratogenic effects, including digital anomalies and ossification of terminal phalanges. Felodipine is a former pregnancy category C drug. According to ACOG( American College of Obstetricians and Gynecologists) guidelines, if calcium channel blockers are used during pregnancy, then felodipine is preferred.[18]

Breastfeeding Considerations: No clinical information is available on using felodipine during breastfeeding. It is not known whether felodipine is present in human milk. There is a potential for serious adverse reactions from felodipine in the infant; hence an alternate drug is preferred.[19]

Pediatric Population: Felodipine is not approved by FDA for pediatric hypertension.[20] However,  according to American Academy of Pediatrics guidelines, the recommended dose of felodipine for age>6 years is 2.5 mg.[21]

Elderly Patients: In patients above 65 years of age, starting them on a low dose of felodipine (2.5 mg) is recommended. While changing the dose of the medication, their blood pressure should undergo strict monitoring.[22]

Adverse Effects

The adverse effects of felodipine classify as either dose-dependent or dose-independent.

  • The common dose-dependent adverse effects of felodipine include peripheral edema, flushing, palpitations, and headaches. The most common clinical side effect of felodipine use is peripheral edema. The frequency of peripheral edema is higher in individuals taking a higher dose of felodipine and elderly individuals. The incidence of peripheral edema is about 30% in elderly patients taking 20 mg of felodipine daily. Felodipine selectively dilates the arterioles, which leads to an increase in intra-capillary pressure, thus causing extravasation of fluid into the interstitial space and resulting in peripheral edema. ACE inhibitors or angiotensin receptor blockers can prevent peripheral edema. Flushing and headaches also occur because of the vasodilatory effects of felodipine. Palpitations may occur because of reflex tachycardia.
  • The dose-independent adverse effects of felodipine include fatigue, nausea, and gingival hyperplasia. Gingival hyperplasia occurs in less than 1% of patients and is more common in individuals with poor dental hygiene. The mechanism of gingival hyperplasia is overexpression of growth factors due to high concentrations of calcium ions (Ca), leading to fibroblast proliferation and chronic inflammatory cell infiltration.[23] Gingival hyperplasia is usually reversible on discontinuation of felodipine.[24]

Drug interactions: Cytochrome P450 3A4 metabolizes felodipine.

  • The plasma level of felodipine increases when used in conjunction with CYP 3A4 inhibitors such as azole antifungals (itraconazole and ketoconazole), macrolide antibiotics (clarithromycin and azithromycin), HIV protease inhibitors, immunosuppressants (cyclosporine), cimetidine, or grapefruit juice.[2]
  • The plasma level and efficacy of felodipine decrease when co-administered with CYP3A4 inducers such as anticonvulsants (phenytoin and carbamazepine), Saint John’s wort, or rifampicin. 
  • When metoprolol is subsequently administered with conventional felodipine formulation in treating essential hypertension, the plasma concentration of metoprolol increases while that of felodipine remains unchanged.
  • If felodipine is co-administered with theophylline, it results in a decrease in the plasma concentration of theophylline.[25]
  • Calcium channel blockers and statins are frequently prescribed in patients with cardiovascular risk factors. In a study, acute kidney injury, hyperkalemia, acute myocardial infarction, and acute ischemic stroke were increased due to interaction between CYP3A4-metabolized statins and CCBs that inhibit CYP3A4, like felodipine.[26]


The absolute contraindication of felodipine use includes hypersensitivity to felodipine or excipients.

The relative contraindications for the use of felodipine include:

  • Liver failure: Patients with liver failure cannot metabolize felodipine resulting in elevated plasma concentration of the medication.
  • Severe hypotension: Dihydropyridine calcium channel antagonists should not be used in patients with severe hypotension as they may precipitate the condition and cause syncope.
  • Acute coronary syndrome: Felodipine has a significant vasodilatory effect, which results in reflex tachycardia, which increases the myocardial oxygen demand and worsens myocardial ischemia.
  • Pregnancy and lactation: In animal studies, felodipine has been shown to cause teratogenic effects, including digital anomalies and ossification of terminal phalanges. It is a former FDA pregnancy category C drug.[19]


It is essential for healthcare personnel and patients to monitor blood pressure and heart rate regularly. Routine laboratory monitoring is not necessary for patients who are taking felodipine. Patients should undergo regular assessment for adverse effects such as peripheral edema, flushing, headache, or dizziness, and the provider should titrate the dose accordingly.[27] Cardiovascular (CV) risk assessment is a contemporary paradigm for stratifying patients with hypertension for clinical management and prevention of cardiovascular disease.[28]


A mild to moderate overdose of felodipine can result in hypotension secondary to peripheral vasodilation and reflex tachycardia. However, a severe overdose of felodipine can cause life-threatening profound hypotension and bradycardia. Case fatality due to profound, refractory circulatory collapse overdose has been reported in the literature.[29] The risk of overdose increases in elderly individuals, patients with liver impairment, and concomitant administration of felodipine with beta-blockers. Overdose symptoms can include lightheadedness, syncope, altered mental status, and shock secondary to profound hypotension. The insulin release from the pancreas depends on calcium influx through the L-type channels. Felodipine blocks these calcium channels and results in hyperglycemia because of decreased insulin release.[30]

The first step in managing felodipine overdose is maintaining a patent airway. Patients who have consumed an excess of felodipine ER tablets but have not yet developed any symptoms should be started on gastrointestinal decontamination with whole bowel irrigation if they present within 6 to 8 hours of drug ingestion. Patients with hypotension should undergo resuscitation with intravenous fluids. However, caution is necessary for individuals with congestive heart failure and pulmonary edema. Vasopressor therapy with dopamine or norepinephrine is an as-need option for hypotension. Intravenous calcium gluconate or calcium chloride (given via central line) are also options in treating felodipine overdose.

In patients with severe overdose, atropine should be administered intravenously for bradycardia. The vital signs, serum electrolytes, especially potassium, blood glucose, urine output, and ECG, should be monitored regularly. Hyperinsulinemia-euglycemia (HIE) therapy is also an established treatment for calcium channel blocker overdose.[31] This therapy helps mobilize glucose from the peripheral tissue to serve as an alternative energy source for the myocardium.[32]

Enhancing Healthcare Team Outcomes

Felodipine ER with once-daily administration is a convenient-to-use anti-hypertensive medication. Healthcare personnel should be aware of the indications and adverse effects of felodipine. The clinicians need to obtain an appropriate medication history to look for drug interactions since felodipine is metabolized by CYP 3A4. The healthcare personnel, including pharmacists, should educate the patients regarding medication adherence and regular blood pressure monitoring. If patients develop symptomatic hypotension,  discontinue the medicine immediately, and the patient should present to the emergency department.

Clinicians (MDs, DOs, NPs, PAs) will decide the dose of felodipine when appropriate. The pharmacist should verify that all dosing suits the clinical scenario and report any discrepancies. The pharmacy should also perform medication reconciliation since, as discussed, felodipine can have significant drug-drug interactions. Nursing will be in charge of administration for inpatients, monitoring the patient on subsequent outpatient visits, monitoring for adverse reactions, medication compliance, and therapy effectiveness, and reporting any adverse findings to the healthcare team.

Felodipine therapy requires an interprofessional team approach, including clinicians(MD, DO, NP, PA), specialists, specialty-trained nurses, and pharmacists, all collaborating to achieve optimal patient results. [Level 5]



9/3/2022 3:18:33 PM



Paz MA,de-La-Sierra A,Sáez M,Barceló MA,Rodríguez JJ,Castro S,Lagarón C,Garrido JM,Vera P,Coll-de-Tuero G, Treatment efficacy of anti-hypertensive drugs in monotherapy or combination: ATOM systematic review and meta-analysis of randomized clinical trials according to PRISMA statement. Medicine. 2016 Jul     [PubMed PMID: 27472680]

Level 1 (high-level) evidence


Todd PA,Faulds D, Felodipine. A review of the pharmacology and therapeutic use of the extended release formulation in cardiovascular disorders. Drugs. 1992 Aug;     [PubMed PMID: 1382018]


Yedinak KC,Lopez LM, Felodipine: a new dihydropyridine calcium-channel antagonist. DICP : the annals of pharmacotherapy. 1991 Nov;     [PubMed PMID: 1763537]


Navadiya K,Tiwari S, Pharmacology, Efficacy and Safety of Felodipine with a Focus on Hypertension and Angina Pectoris. Current drug safety. 2015     [PubMed PMID: 25973793]


Anand I, Stable but Progressive Nature of Heart Failure: Considerations for Primary Care Physicians. American journal of cardiovascular drugs : drugs, devices, and other interventions. 2018 Oct     [PubMed PMID: 29761293]


Hornum M,Iversen M,Oturai P,Andersen MJ,Zemtsovski M,Bredahl P,Bjarnason NH,Christensen KB,Carlsen J,Møller CH,Feldt-Rasmussen B,Perch M, Felodipine and renal function in lung transplantation: A randomized placebo-controlled trial. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2020 Jun;     [PubMed PMID: 32061508]

Level 1 (high-level) evidence


Tanaka KI,Niino T,Ishihara T,Takafuji A,Takayama T,Kanda Y,Sugizaki T,Tamura F,Kurotsu S,Kawahara M,Mizushima T, Protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice. Scientific reports. 2017 Jun 13     [PubMed PMID: 28611390]


Katz AM, Pharmacology and mechanisms of action of calcium-channel blockers. Journal of clinical hypertension. 1986 Sep;     [PubMed PMID: 3540226]


Dhein S,Salameh A,Berkels R,Klaus W, Dual mode of action of dihydropyridine calcium antagonists: a role for nitric oxide. Drugs. 1999 Sep;     [PubMed PMID: 10493269]


Bailey DG,Dresser G,Arnold JM, Grapefruit-medication interactions: forbidden fruit or avoidable consequences? CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2013 Mar 5     [PubMed PMID: 23184849]


Fagerberg JH,Sjögren E,Bergström CAS, Concomitant intake of alcohol may increase the absorption of poorly soluble drugs. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2015 Jan 25     [PubMed PMID: 25444841]


Snyder BD,Rowland A,Polasek TM,Miners JO,Doogue MP, Evaluation of felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions. European journal of clinical pharmacology. 2014 Sep     [PubMed PMID: 25028073]


Felodipine LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012     [PubMed PMID: 31643617]


Hsiao CL,Wu YC,Hsu KY, Pharmacokinetics of felodipine extended-release tablets in healthy Taiwanese subjects: a retrospective review. Arzneimittel-Forschung. 2011;     [PubMed PMID: 21950148]

Level 2 (mid-level) evidence


Dunselman PH,Edgar B, Felodipine clinical pharmacokinetics. Clinical pharmacokinetics. 1991 Dec;     [PubMed PMID: 1782737]


Regårdh CG,Edgar B,Olsson R,Kendall M,Collste P,Shansky C, Pharmacokinetics of felodipine in patients with liver disease. European journal of clinical pharmacology. 1989;     [PubMed PMID: 2753065]


Larsson R,Karlberg BE,Gelin A,Aberg J,Regårdh CG, Acute and steady-state pharmacokinetics and antihypertensive effects of felodipine in patients with normal and impaired renal function. Journal of clinical pharmacology. 1990 Nov;     [PubMed PMID: 2243149]


American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 203: Chronic Hypertension in Pregnancy. Obstetrics and gynecology. 2019 Jan:133(1):e26-e50. doi: 10.1097/AOG.0000000000003020. Epub     [PubMed PMID: 30575676]


Felodipine Drugs and Lactation Database (LactMed). 2006     [PubMed PMID: 29999713]


Chu PY,Campbell MJ,Miller SG,Hill KD, Anti-hypertensive drugs in children and adolescents. World journal of cardiology. 2014 May 26     [PubMed PMID: 24944754]


Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, de Ferranti SD, Dionne JM, Falkner B, Flinn SK, Gidding SS, Goodwin C, Leu MG, Powers ME, Rea C, Samuels J, Simasek M, Thaker VV, Urbina EM, SUBCOMMITTEE ON SCREENING AND MANAGEMENT OF HIGH BLOOD PRESSURE IN CHILDREN. Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents. Pediatrics. 2017 Sep:140(3):. pii: e20171904. doi: 10.1542/peds.2017-1904. Epub 2017 Aug 21     [PubMed PMID: 28827377]

Level 1 (high-level) evidence


van Ree JW,van der Pol GA, Low dosages of felodipine ER once daily as monotherapy in elderly hypertensive patients: effect on ambulatory blood pressure and quality of life. Journal of human hypertension. 1996 Sep;     [PubMed PMID: 8953207]

Level 2 (mid-level) evidence


Elmfeldt D,Hedner T,Westerling S, Felodipine in hypertension--a review. Journal of cardiovascular pharmacology. 1987;     [PubMed PMID: 2442509]


Khzam N,Bailey D,Yie HS,Bakr MM, Gingival Enlargement Induced by Felodipine Resolves with a Conventional Periodontal Treatment and Drug Modification. Case reports in dentistry. 2016     [PubMed PMID: 27034854]

Level 3 (low-level) evidence


Bratel T,Billing B,Dahlqvist R, Felodipine reduces the absorption of theophylline in man. European journal of clinical pharmacology. 1989;     [PubMed PMID: 2753066]


Wang YC,Hsieh TC,Chou CL,Wu JL,Fang TC, Risks of Adverse Events Following Coprescription of Statins and Calcium Channel Blockers: A Nationwide Population-Based Study. Medicine. 2016 Jan     [PubMed PMID: 26765458]


Calcium Channel Blockers LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012     [PubMed PMID: 31643892]


Wang MC,Lloyd-Jones DM, Cardiovascular Risk Assessment in Hypertensive Patients. American journal of hypertension. 2021 Jun 22     [PubMed PMID: 33503227]


Lota H,Powell N,Negus R,Leonard R,Manikon M, A case of fatal felodipine overdose. Acute medicine. 2008;     [PubMed PMID: 21607228]

Level 3 (low-level) evidence


Proano L,Chiang WK,Wang RY, Calcium channel blocker overdose. The American journal of emergency medicine. 1995 Jul;     [PubMed PMID: 7605536]


Greene SL,Gawarammana I,Wood DM,Jones AL,Dargan PI, Relative safety of hyperinsulinaemia/euglycaemia therapy in the management of calcium channel blocker overdose: a prospective observational study. Intensive care medicine. 2007 Nov     [PubMed PMID: 17622512]

Level 2 (mid-level) evidence


Burkes R,Wendorf G, A multifaceted approach to calcium channel blocker overdose: a case report and literature review. Clinical case reports. 2015 Jul     [PubMed PMID: 26273444]

Level 3 (low-level) evidence