Felodipine

C08C - Selective calcium channel blockers with mainly vascular effects ATC C08CA02 Small molecule approved 1991 Oral Natural product

JFDA label: PLENDIL TAB

Mechanism of Action

Antagonist of Mineralocorticoid receptor — Mineralocorticoid receptor antagonist; Blocker of Voltage-gated L-type calcium channel — Voltage-gated L-type calcium channel blocker

Target	Action	Gene / class
Mineralocorticoid receptor efficacy	ANTAGONIST	NR3C2
Voltage-gated L-type calcium channel efficacy	BLOCKER

Indications

Approved

Chronic kidney disease (CKD) and hypertension
Diabetes and hypertension
Hypertension

Off-label

Pediatric hypertension

Contraindications

Source: Lexicomp

Additional contraindications (not in U.S. labeling): Hypersensitivity to other dihydropyridines Absolute
Hypersensitivity to felodipine or any component of the formulation Absolute
women of childbearing potential, in pregnancy, and during lactation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (1)

Very Common Peripheral edema

Nervous system disorders (1)

Very Common Headache

Other (2)

Common Cardiovascular: Flushing · tachycardia

Dosing

Source: Lexicomp

Hypertension: Oral: Initial: 5 mg once daily; adjust dose as needed at no less than 2-week intervals. Usual dose range: 5 to 10 once daily (ASH/ISH [Weber, 2014]) although some patients may benefit from 2.5 mg once daily. Doses >10 mg daily are associated with greater antihypertensive effects but also a large increase in the incidence of peripheral edema and other vasodilatory adverse effects.

(For additional information see "Felodipine: Pediatric drug information") Hypertension: Children ≥6 years and Adolescents (off-label use): Oral: Initial: 2.5 mg once daily; may increase as needed at no less than 2-week intervals to a maximum of 10 mg once daily (NHLBI, 2011)

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). The Canadian labeling recommends a maximum dose of 10 mg daily.

No dosage adjustment necessary.

Initial: 2.5 mg once daily; monitor blood pressure closely during titration. The Canadian labeling recommends a maximum dose of 10 mg daily.

Warnings & Precautions

Source: Lexicomp

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 ACCF/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 (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. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events were observed in animal reproduction studies. Untreated chronic maternal hypertension is associated with adverse events in the fetus, infant, and mother. If treatment for hypertension during pregnancy is needed, other agents are preferred (ACOG, 2013). The Canadian labeling contraindicates use in women of childbearing potential and during pregnancy.

Lactation

It is not known if felodipine is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, the U.S. labeling recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother. The Canadian labeling contraindicates use in nursing women.

Chemistry & Properties

Formula	C18H19Cl2NO4
Molecular weight	384.26 g/mol
IUPAC name	5-O-ethyl 3-O-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
CAS	72509-76-3
PubChem CID	3333
InChIKey	`RZTAMFZIAATZDJ-UHFFFAOYSA-N`
logP	3.96 (XLogP 3.9)
Polar surface area	64.63 Å²
H-bond acceptors / donors	5 / 1
Drug-likeness (QED)	0.80
Lipinski violations	0

SMILES

CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1c1cccc(Cl)c1Cl

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Inhibitor	—
CYP1A2	Substrate	—
CYP2B6	Inhibitor	—
CYP2C19	Inhibitor	—
CYP2C19	Substrate	—
CYP2C8	Inhibitor	—
CYP2C9	Inhibitor	IC₅₀ 4.5794999999999995 µM
CYP3A4	Inhibitor	—
CYP3A4	Substrate	—

Receptor binding (top 2)

Target	Action	Affinity
CFTR (CFTR)	Activator	pKi 8.4
CFTR (CFTR)	Activator	pEC50 5.7

Transporters

ASBT (Inhibitor)BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)ENT1 (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP2B1 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)Transporter(unspecified) (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Apalutamide	major
Betrixaban	major
Ceritinib	major
Dolasetron	major
Edoxaban	major
Enzalutamide	major
Ketoconazole	major
Lumacaftor	major
Mitotane	major
Siponimod	major
Venetoclax	major
Acetylsalicylic acid	moderate
Adalimumab	moderate
Afatinib	moderate
Aldesleukin	moderate
Alefacept	moderate
Alimemazine	moderate
Amifostine	moderate
Anakinra	moderate
Apixaban	moderate
Aprepitant	moderate
Betamethasone	moderate
Bexarotene	moderate
Binimetinib	moderate
Brigatinib	moderate
Brimonidine (ophthalmic)	moderate
Brimonidine (topical)	moderate
Budesonide	moderate
Bupropion	moderate
Calcium Phosphate	moderate
Calcium acetate	moderate
Calcium carbonate	moderate
Calcium chloride	moderate
Calcium citrate	moderate
Calcium glubionate anhydrous	moderate
Calcium glucoheptonate	moderate
Calcium gluconate	moderate
Calcium lactate	moderate
Canagliflozin	moderate
Canakinumab	moderate

Showing 40 of 100+.

Registered Products (2)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
PLENDIL TAB	Tablet 5 mg	30 tab	Shawi & Rushedat Drug Store	4.150
PLENDIL TAB	Tablet 10 mg	30 tab	Shawi & Rushedat Drug Store	7.490