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7/19/2019 10:06:28 PM


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]

Non-FDA approved uses of felodipine:

  • Chronic stable angina pectoris
  • Congestive heart failure
  • Renovascular hypertension
  • Pulmonary hypertension

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. The binding of cytosolic calcium to calmodulin follows this action resulting in the activation of myosin light-chain kinase (MLCK). The activated MLCK phosphorylates myosin light-chain resulting in the attachment of 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.[3] 

Felodipine, like the other dihydropyridine calcium-channel blockers, blocks the voltage-dependent L-type calcium channels and prevents the entry of calcium into the smooth muscle cell. Reduced cytosolic calcium results in a decrease in peripheral vascular resistance, vasodilation, and ultimately 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.[4]

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


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 as an extended-release (ER) tablet formulation. The ER formulation offers several benefits, including once-daily dosing, minimal drug interactions, and lesser adverse effects. It is recommended to start the patient on a 5 mg dose of felodipine ER once daily. 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.


Felodipine is almost completely absorbed after oral administration. However, the bioavailability is only about 20% because of extensive first-pass metabolism of felodipine. The plasma concentration of felodipine increases when administered along with high fat or high carbohydrate diet. Felodipine is highly protein-bound and has a high volume of distribution.[5]

The utility of felodipine in special population groups:

Pediatric population: Felodipine should not be used in pediatric patients since there has been no assessment of its safety and efficacy. 

Pregnancy: Felodipine should is contraindicated in pregnant patients.

Elderly patients: In patients above 65 years of age, it is recommended to start them on a low dose of felodipine (2.5 mg). While changing the dose of the medication, their blood pressure should undergo strict monitoring.[6]

Hepatic impairment: Patients with liver impairment have higher plasma concentration of felodipine since it undergoes hepatic metabolism. It is not recommended to use felodipine in patients with hepatic impairment.[7]

Renal impairment: Felodipine is safe for use in patients with renal failure.[8]

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.[1]

The plasma level and efficacy of felodipine decrease when it is 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 the treatment of essential hypertension, the plasma level 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.[9]

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 in 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 lead 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 the 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.[10]


The absolute contraindication of felodipine use includes hypersensitivity to felodipine or its ingredients.

The relative contraindications for the use of felodipine include:

  • Pregnancy: In animal studies, felodipine has been shown to cause teratogenic effects, including digital anomalies and ossification of terminal phalanges. It is a pregnancy category C drug.
  • Liver failure: Patients with liver failure are unable to 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.


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.


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. The risk of overdose increases in elderly individuals, patients with liver impairment, and concomitant administration of felodipine with beta-blockers. Symptoms of overdose can include lightheadedness, syncope, altered mental status, and shock secondary to profound hypotension. The release of insulin from the pancreas depends on the influx of calcium through the L-type channels. Felodipine blocks these calcium channels and results in hyperglycemia because of decreased insulin release.[11] 

The first step in the management of felodipine overdose is to maintain a patent airway. In patients who have consumed an excess of felodipine ER tablets but have not yet developed any symptoms, they 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 the treatment of 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 modality of treatment for calcium channel blocker overdose.[12] This therapy helps to mobilize glucose from the peripheral tissue to serve as an alternative source of energy for the myocardium.  

Enhancing Healthcare Team Outcomes

Felodipine ER with once-daily administration is convenient to use anti-hypertensive medication. Healthcare personnel should be aware of the indications and adverse effects of felodipine. The physicians 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 monitoring of blood pressure. If patients develop symptomatic hypotension, the medication should be discontinued immediately, and the patient should present to the emergency department.

Clinicians (MDs, DOs, NPs, PAs) will make the decision to dose felodipine when appropriate. The pharmacist should verify all dosing is suitable for the clinical scenario, and report back 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, and will see the patient on subsequent outpatient visits, and can monitor for adverse reactions as well as medication compliance and therapy effectiveness, reporting back to the healthcare team any adverse findings.

Felodipine therapy requires an interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient results. [Level V]

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Felodipine - Questions

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A 56-year old male presents with complaints of palpitations and swelling over both his legs since the past week. His past medical history is significant for hypertension, diabetes and GERD. He is currently taking metformin, felodipine, and pantoprozole. A month back, the patient had a rash and itching over his left upper arm. The patient described the rash as a red circular border with central clearing. The provider at that time had started him on anti-fungal medication. On examination, there is resolution of the rash and peripheral edema is present. His blood pressure is 140/90 mm Hg and pulse is 80/min. Which of the following is most likely responsible for the patient's complaints?

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A 45-year old male presents with complaints of swelling over both the legs for the last 2 weeks. The swelling has been increasing since the past week. His past medical history is significant for diabetes for the past 10 years, hypothyroidism, and hypertension for 5 years. His family history is significant for hypertension in his father and myocardial infarction in his mother. His current medications include metformin, felodipine, atorvastatin, and levothyroxine. Which of the following is responsible for swelling over his legs?

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A 68-year old male presents with abdominal swelling of one-week duration. The swelling has progressed, and the patient also has swelling over bilateral lower limbs. He has chronic alcohol use disorder with a CAGE score 3. His past medical history is significant for diabetes, hypertension, and chronic kidney disease with a baseline serum creatinine 2.8 mg/dl. His current medications include metformin, felodipine, and atorvastatin. On examination, there is bilateral pedal edema, and varices are present over his abdomen. His blood pressure is 130/80 mm Hg, and his pulse is 90/min. His blood investigations reveal the following: random blood glucose 130 mg/dl, BUN 60 mg/dl, and serum creatinine 2.7 mg/dl. Abdominal ultrasound reveals a fibrotic liver with regenerative nodules. Which of the following represents an indication to change his antihypertensive medication?

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A 65-year-old male presents to the office for a regular health examination. His past medical history is significant for hypothyroidism for which he was started on levothyroxine. However, the patient has been not compliant with his medication. During his routine examination, his repeat blood pressure is 142/92 mm Hg, and his pulse is 70 bpm. The patient mentions that he does not like taking a lot of tablets. Keeping this in mind, the provider decides to start the patient on extended-release felodipine 5 mg therapy once daily. Which of the following describes the mechanism of action of this therapy?

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Felodipine - References


Bratel T,Billing B,Dahlqvist R, Felodipine reduces the absorption of theophylline in man. European journal of clinical pharmacology. 1989;     [PubMed]
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]
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]
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]
Dunselman PH,Edgar B, Felodipine clinical pharmacokinetics. Clinical pharmacokinetics. 1991 Dec;     [PubMed]
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]
Elmfeldt D,Hedner T,Westerling S, Felodipine in hypertension--a review. Journal of cardiovascular pharmacology. 1987;     [PubMed]
Katz AM, Pharmacology and mechanisms of action of calcium-channel blockers. Journal of clinical hypertension. 1986 Sep;     [PubMed]
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]
Yedinak KC,Lopez LM, Felodipine: a new dihydropyridine calcium-channel antagonist. DICP : the annals of pharmacotherapy. 1991 Nov;     [PubMed]
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]
Proano L,Chiang WK,Wang RY, Calcium channel blocker overdose. The American journal of emergency medicine. 1995 Jul;     [PubMed]


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