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Felodipine

Class: Dihydropyridines
- Calcium-Channel Blocking Agents, Dihydropyridine
- Calcium Antagonists
VA Class: CV200
Chemical Name: 4-(2,3-Dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5 -pyridinedicarboxylic acid ethyl methyl ester
Molecular Formula: C18H19Cl2NO4
CAS Number: 72509-76-3
Brands: Plendil

Medically reviewed by Drugs.com. Last updated on Mar 18, 2019.

Introduction

Calcium-channel blocking agent; a 1,4-dihydropyridine derivative.1 2

Uses for Felodipine

Hypertension

Management of hypertension alone or in combination with other classes of antihypertensive agents.1 2 3 1200

Calcium-channel blockers are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics.501 502 503 504 1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501 502 503 504 1200 1213

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).501 502 503 504 515 1200 1201

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (See Table 1.)

Source: 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. Hypertension. 2018;71:e13-115.</

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.501 503 504 505 506 507 508 515 523 526 530 1200 1201 1207 1209 1222 1223 1229

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, an SBP goal of <130 mm Hg is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210

Other hypertension guidelines generally based target BP goals on age and comorbidities.501 504 536 Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients501 504 536 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.1222 1223 1224 1229

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.1200 1220 1229

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.1200

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).1200

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.1200

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.1200 Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.502 1200

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.1200 Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200

Calcium-channel blockers may be beneficial in hypertensive patients with certain coexisting conditions (e.g., ischemic heart disease)523 and in geriatric patients, including those with isolated systolic hypertension.502 510 1200

Calcium-channel blockers may be particularly useful in black patients with hypertension;81 82 1250 1251 1252 1253 1254 1255 such patients generally respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to other antihypertensive drug classes (e.g., ACE inhibitors, angiotensin II receptor antagonists).501 504 1200 However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.1200

Felodipine Dosage and Administration

General

BP Monitoring and Treatment Goals

  • Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.1200

  • If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.1200 1216

  • If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., ACE inhibitor, angiotensin II receptor antagonist, thiazide diuretic).1200 1216

  • Many patients will require at least 2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved with 2 antihypertensive agents, add a third drug.1200 1216 1220

Administration

Oral Administration

Administer once daily without food or with a light meal.1 Avoid concomitant administration with grapefruit juice.1 (See Specific Drugs and Foods under Interactions.)

Swallow extended-release tablets intact; do not chew or crush.1

Dosage

Pediatric Patients

Hypertension
Oral

Children ≥6 years of age: Some experts recommend an initial dosage of 2.5 mg once daily.1150 Experts state that dosage may be increased every 2–4 weeks until BP controlled, maximum dosage reached (10 mg once daily), or adverse effects occur.1150

Adults

Hypertension
Oral

Initially, 2.5–5 mg once daily.1

Usual maintenance dosage: 2.5–10 mg daily.1 1200 Dosages >10 mg daily associated with increased BP response but also with exaggerated adverse vasodilatory effects (e.g., peripheral edema).1

Prescribing Limits

Pediatric Patients

Hypertension
Oral

Maximum 10 mg of felodipine daily.1150

Special Populations

Hepatic Impairment

Usual initial dosage: 2.5 mg daily.1 68 Closely monitor BP response with each dosage adjustment.1

Renal Impairment

Dosage adjustment generally not required.1

Geriatric Patients

Usual initial dosage: 2.5 mg daily.1 68 Closely monitor BP response with each dosage adjustment.1

Risk of peripheral edema increased substantially with dosages >10 mg daily.1

Cautions for Felodipine

Contraindications

  • Known hypersensitivity to felodipine or any ingredient in the formulation.1

Warnings/Precautions

General Precautions

Angina

Possible hypotension and/or syncope resulting in reflex tachycardia and precipitation of angina pectoris in susceptible patients.1

Heart Failure

Safety not established in patients with heart failure; use with caution in patients with heart failure or compromised ventricular function, particularly when used in combination with a β-adrenergic blocker.1

Peripheral Edema

Mild peripheral edema possible within 2–3 weeks of initiating therapy, particularly in older patients (e.g., >60 years of age) receiving higher felodipine dosages (e.g., 20 mg daily).1

Specific Populations

Pregnancy

Felodipine: Category C.1

Lactation

Not known whether felodipine is distributed into milk; discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy remain to be fully established in children;1 however, some experts have recommended dosages for hypertension based on clinical experience.1150

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution.1 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Felodipine clearance may be decreased.1 (See Special Populations under Pharmacokinetics.) Manufacturer recommends lower initial dosage in patients with hepatic impairment.1 (See Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

Peripheral edema, headache, flushing.1

Interactions for Felodipine

Metabolized by CYP3A4.1

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors: Potential for increased plasma felodipine concentrations, with possible reduction in BP and increase in heart rate; use with caution.1

Specific Drugs and Foods

Drug or Food

Interaction

Comment

Anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin)

Decreased plasma felodipine concentrations1

Consider use of alternative antihypertensive agents1

Antifungals, azoles (itraconazole, ketoconazole)

Increased plasma felodipine concentrations; decreased BP and increased heart rate reported with itraconazole1

Cimetidine

Increased plasma felodipine concentrations1

Digoxin

Pharmacokinetic interaction unlikely1

Erythromycin

Increased plasma felodipine concentrations1

Grapefruit juice

Increased oral bioavailability of felodipine1

Avoid concomitant use1

Indomethacin

Pharmacokinetic interaction unlikely1

Metoprolol

Increased plasma metoprolol concentrations1

Not considered clinically important1

Orange juice

Pharmacokinetic interaction unlikely1

Spironolactone

Pharmacokinetic interaction unlikely1

Tacrolimus

Increased plasma tacrolimus concentrations1

Monitor plasma tacrolimus concentrations1

Felodipine Pharmacokinetics

Absorption

Bioavailability

Almost completely absorbed following oral administration but undergoes extensive first-pass metabolism.1

Systemic bioavailability of felodipine is approximately 20%.1

Onset

Antihypertensive effect evident within 2–5 hours.1

Duration

During chronic administration, substantial BP control lasts for 24 hours, with trough reductions in DBP approximately 40–50% of peak reductions.1

Food

High-fat or high-carbohydrate meal increases peak plasma concentrations but does not affect extent of absorption.1 A light meal (e.g., orange juice, toast, and cereal) does not alter felodipine pharmacokinetics.1

Distribution

Extent

Crosses the blood-brain barrier.51

Crosses the placenta in animals.1

Plasma Protein Binding

>99%.1

Elimination

Metabolism

Metabolized in the liver by CYP3A4.1

None of the 6 metabolites identified to date has substantial vasodilating activity.1

Elimination Route

Eliminated as metabolites, mainly in urine and to a lesser extent in feces.1

Half-life

Mean terminal half-life is approximately 11–16 hours following administration as an immediate-release formulation.1

Special Populations

Hepatic impairment: Clearance is decreased to about 60% of that observed in young healthy individuals.1

Geriatric patients: Felodipine clearance is decreased to about 45% of that observed in young healthy individuals.1

Stability

Storage

Oral

Tablets

Tightly closed container at <30°C.1 Protect from light.1

Actions

  • Inhibits the transmembrane influx of extracellular calcium ions across the membranes of myocardial cells and vascular smooth muscle cells, without changing serum calcium concentrations.c

  • Hypotensive effect is principally a consequence of a dose-related reduction in peripheral vascular resistance, with a modest reflex increase in heart rate.1

  • Negative inotropic effects observed in vitro but not in intact animals.1

  • Has no substantial effect on cardiac conduction (PR, PQ, and HV intervals).1

Advice to Patients

  • Risk of mild gingival hyperplasia; importance of good dental hygiene.1

  • Importance of taking felodipine exactly as prescribed.1

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Felodipine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release

2.5 mg*

Felodipine Extended-release Tablets

Plendil

AstraZeneca

5 mg*

Felodipine Extended-release Tablets

Plendil

AstraZeneca

10 mg*

Felodipine Extended-release Tablets

Plendil

AstraZeneca

AHFS DI Essentials™. © Copyright 2019, Selected Revisions March 18, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. AstraZeneca LP. Plendil (felodipine) extended-release tablets prescribing information. Wayne, PA; 2003 Nov.

2. Saltiel E, Ellrodt AG, Monk JP et al. Felodipine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension. Drugs. 1988; 36:387-428. http://www.ncbi.nlm.nih.gov/pubmed/3069435?dopt=AbstractPlus

3. Yedinak KC, Lopez LM. Felodipine: a new dihydropyridine calcium-channel antagonist. DICP. 1991; 25:1193-206. http://www.ncbi.nlm.nih.gov/pubmed/1763537?dopt=AbstractPlus

5. Anon. Drugs for hypertension. Med Lett Drugs Ther. 1984; 26:107-12. http://www.ncbi.nlm.nih.gov/pubmed/6150424?dopt=AbstractPlus

7. Reviewers’ comments (personal observations).

8. Bailey DG, Spence JD, Munoz C et al. Interaction of citrus juices with felodipine and nifedipine. Lancet. 1991; 337:268-9. http://www.ncbi.nlm.nih.gov/pubmed/1671113?dopt=AbstractPlus

10. Sandoz Pharmaceuticals Corp. DynaCirc (isradipine) capsules prescribing information. East Hanover, NJ; 1992 Jun.

11. Lopez LM, Santiago TM. Isradipine—another calcium-channel blocker for the treatment of hypertension and angina. Ann Pharmacother. 1992; 26:789-99. http://www.ncbi.nlm.nih.gov/pubmed/1535246?dopt=AbstractPlus

12. Fitton A, Benfield P. Isradipine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cardiovascular disease. Drugs. 1990; 40:31-74. http://www.ncbi.nlm.nih.gov/pubmed/2143980?dopt=AbstractPlus

13. Walton T, Symes LR. Felodipine and isradipine: new calcium-channel blocking agents for the treatment of hypertension. Clin Pharm. 1993; 12:261-75. http://www.ncbi.nlm.nih.gov/pubmed/8458178?dopt=AbstractPlus

14. Prisant LM, Carr AA, Nelson EB et al. Isradipine vs propranolol in hydrochlorothiazide-treated hypertensives: a multicenter evaluation. Arch Intern Med. 1989; 149:2453-7. http://www.ncbi.nlm.nih.gov/pubmed/2530945?dopt=AbstractPlus

15. Anon. Isradipine for hypertension. Med Lett Drugs Ther. 1991; 33:51-4. http://www.ncbi.nlm.nih.gov/pubmed/1827655?dopt=AbstractPlus

16. Alderman MH. Which antihypertensive drugs first—and why! JAMA. 1992; 267:2786-7. Editorial.

17. Weber MA, Laragh JH. Hypertension: steps forward and steps backward: the Joint National Committee fifth report. Arch Intern Med. 1993; 153:149-52. http://www.ncbi.nlm.nih.gov/pubmed/8422205?dopt=AbstractPlus

18. Glasser SP, Clark PI, Lipicky RJ et al. Exposing patients with chronic, stable, exertional angina to placebo periods in drug trials. JAMA. 1991; 265:1550-4. http://www.ncbi.nlm.nih.gov/pubmed/1671885?dopt=AbstractPlus

19. National Heart, Lung, and Blood Institute. NHLBI panel reviews safety of calcium channel blockers. Rockville, MD; 1995 Aug 31. Press release.

20. National Heart, Lung, and Blood Institute. New analysis regarding the safety of calcium-channel blockers: a statement for health professionals from the National Heart, Lung, and Blood Institute. Rockville, MD; 1995 Sep 1.

21. Anon. NHLBI panel stands by JNC V in response to Circulation CCB article; AIM report supports use of beta blockers for prevention of sudden cardiac death. F-D-C Rep. 1995; 57(Sep 4):3-4.

22. American Heart Association. Public advisory statement on calcium channel blocker drugs. Dallas, TX; 1995 Aug 28.

23. Psaty BM, Heckbert SR, Koepsell TD et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA. 1995; 274:620-5. http://www.ncbi.nlm.nih.gov/pubmed/7637142?dopt=AbstractPlus

24. Psaty BM, Heckbert SR, Koepsell TD et al. The risk of incident myocardial infarction associated with anti-hypertensive drug therapies. Circulation. 1995; 91:925.

25. Buring JE, Glynn RJ, Hennekens CH. Calcium channel blockers and myocardial infarction: a hypothesis formulated but not yet tested. JAMA. 1995; 274:654-5. http://www.ncbi.nlm.nih.gov/pubmed/7637148?dopt=AbstractPlus

26. Furberg CD, Psaty BM, Meyer JV. Nifedipine: dose-related increase in mortality in patients with coronary heart disease. Circulation. 1995; 92:1326-31. http://www.ncbi.nlm.nih.gov/pubmed/7648682?dopt=AbstractPlus

27. Opie LH, Messerli FH. Nifedipine and mortality: grave defects in the dossier. Circulation. 1995; 92:1068-73. http://www.ncbi.nlm.nih.gov/pubmed/7648646?dopt=AbstractPlus

28. Kloner RA. Nifedipine in ischemic heart disease. Circulation. 1995; 92:1074-8. http://www.ncbi.nlm.nih.gov/pubmed/7648647?dopt=AbstractPlus

29. Yusuf S. Calcium antagonists in coronary artery disease and hypertension: time for reevaluation? Circulation. 1995; 92:1079-82. Editorial.

30. Lenfant C. The calcium channel blocker scare: lessons for the future. Circulation. 1995; 91:2855-6. http://www.ncbi.nlm.nih.gov/pubmed/7796490?dopt=AbstractPlus

31. Habib GB. Are calcium antagonists harmful in hypertensive patients? Distinguishing hype from reality. Chest. 1995; 108:3-5. http://www.ncbi.nlm.nih.gov/pubmed/7606987?dopt=AbstractPlus

32. Horton R. Spinning the risks and benefits of calcium antagonists. Lancet. 1995; 346:586-7. http://www.ncbi.nlm.nih.gov/pubmed/7650997?dopt=AbstractPlus

33. Yusuf S, Held P, Furberg C. Update of effects of calcium antagonists in myocardial infarction or angina in light of the Second Danish Verapamil Infarction Trial (DAVIT-II) and other recent studies. Am J Cardiol. 1991; 67:1295-7. http://www.ncbi.nlm.nih.gov/pubmed/2035457?dopt=AbstractPlus

34. Egstrup K, Andersen PE Jr. Transient myocardial ischemia during nifedipine therapy in stable angina pectoris, and its relation to coronary collateral flow and comparison with metoprolol. Am J Cardiol. 1993; 71:177-83. http://www.ncbi.nlm.nih.gov/pubmed/8421980?dopt=AbstractPlus

35. Wagenknecht LE, Furberg CD, Hammon JW et al. Surgical bleeding: unexpected effect of a calcium antagonist. BMJ. 1995; 310:776-7. http://www.ncbi.nlm.nih.gov/pubmed/7711582?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2549165&blobtype=pdf

36. Miles Inc. American Heart Association, Dr. Psaty and Miles Inc. release statements qualifying possible risks of calcium channel blockers. West Haven, CT; 1995 Mar 15. Press release.

37. Dear healthcare professional letter regarding calcium-channel blockers and increased risk of heart attack. Chicago:Searle. 1995 Mar 17.

38. McClellan K. Unexpected results from MIDAS in atherosclerosis. Inpharma Wkly. 1994; Apr 9:4.

39. Anon. Groups act to dispel concerns about calcium-channel blockers. Am J Health-Syst Pharm. 1995; 52:1154, 1158. http://www.ncbi.nlm.nih.gov/pubmed/7656105?dopt=AbstractPlus

40. Waters D. Proischemic complications of dihydropyridine calcium channel blockers. Circulation. 1991; 84:2598-600. http://www.ncbi.nlm.nih.gov/pubmed/1959210?dopt=AbstractPlus

41. Messerli FH. Case-control study, meta-analysis, and bouillabaisse: putting the calcium antagonist scare into context. Ann Intern Med. 1995; 123:888-9. http://www.ncbi.nlm.nih.gov/pubmed/7486476?dopt=AbstractPlus

42. Reviewers’ comments (personal observations).

43. Pratt Pharmaceuticals. Procardia (nifedipine) capsules prescribing information (dated 1993 Feb). In: Physicians’ desk reference. 49th ed. Montvale, NJ: Medical Economics Company Inc; 1995:1906-7.

44. Held PH, Yusuf S, Furberg CD. Calcium channel blockers in acute myocardial infarction and unstable angina: an overview. BMJ. 1989; 299:1187-92. http://www.ncbi.nlm.nih.gov/pubmed/2513047?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1838102&blobtype=pdf

45. Bailey DG, Arnold JMO, Spence JD. Grapefruit juice and drugs: how significant is the interaction? Clin Pharmcokinet. 1994; 26:91-8.

47. Kaplan NM. Choice of initial therapy for hypertension. JAMA. 1996; 275:1577-80. http://www.ncbi.nlm.nih.gov/pubmed/8622249?dopt=AbstractPlus

48. Psaty BM, Smith NL, Siscovich DS et al. Health outcomes associated with antihypertensive therapies used as first-line agents: a systematic review and meta-analysis. JAMA. 1997; 277:739-45. http://www.ncbi.nlm.nih.gov/pubmed/9042847?dopt=AbstractPlus

51. AstraZeneca LP. Lexxel (enalapril maleate/felodipine) extended-release tablets prescribing information. Wilmington, DE; 2007 Mar.

52. Gradman AH, Cutler NR, Davis PJ et al. Combined enalapril and felodipine extended release (ER) for systemic hypertension. Am J Cardiol. 1997; 9:431-5.

53. Bailey DG, Arnold JMO, Bend JR et al. Grapefruit juice–felodipine interaction: reproducibitlity and characterization with the extended release drug formulation. Br J Clin Pharmacol. 1995; 40:135-40. http://www.ncbi.nlm.nih.gov/pubmed/8562295?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1365172&blobtype=pdf

54. Velussi M, Brocco E, Frigato F et al. Effects of cilazapril and amlodipine on kidney function in hypertensive NIDDM patients. Diabetes. 1996; 45:216-22. http://www.ncbi.nlm.nih.gov/pubmed/8549868?dopt=AbstractPlus

55. Estacio RO, Jeffers BW, Hiatt WR et al. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. N Engl J Med. 1998; 338:645-52. http://www.ncbi.nlm.nih.gov/pubmed/9486993?dopt=AbstractPlus

56. Pahor M, Psaty BM, Furberg CD. Treatment of hypertensive patients with diabetes. Lancet. 1998; 351:689-90. http://www.ncbi.nlm.nih.gov/pubmed/9504510?dopt=AbstractPlus

57. Tatti P, Pahor M, Byington RP et al. Outcome results of the Fosinopril versus Amlodipine Cardiovascular Events randomized Trial (FACET) in patients with hypertension and NIDDM. Diabetes Care. 1998; 21:597-603. http://www.ncbi.nlm.nih.gov/pubmed/9571349?dopt=AbstractPlus

58. Byington RP, Craven TE, Furberg CD et al. Isradipine, raised glycosylated haemoglobin, and risk of cardiovascular events. Lancet. 1997; 350:1075-6. http://www.ncbi.nlm.nih.gov/pubmed/10213554?dopt=AbstractPlus

59. Alderman M, Madhavan S, Cohen H. Calcium antagonists and cardiovascular events in patients with hypertension and diabetes. Lancet. 1998; 351:216-7. http://www.ncbi.nlm.nih.gov/pubmed/9449897?dopt=AbstractPlus

60. Josefson D. Infarction risk found with calcium channel blocker. BMJ. 1998; 316:797.

61. Cutler JA. Calcium-channel blockers for hypertension—uncertainty continues. N Engl J Med. 1998; 338:679-81. http://www.ncbi.nlm.nih.gov/pubmed/9486999?dopt=AbstractPlus

62. Bayer, West Haven, CT: Personal communication.

63. Bakris GL, Copley JB, Vicknair N et al. Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. Kidney Int. 1996; 50:1641-50. http://www.ncbi.nlm.nih.gov/pubmed/8914031?dopt=AbstractPlus

64. Ameer B, Weintraub RA. Drug interactions with grapefruit juice. Clin Phramacokinet. 1997; 33:103-21.

65. Roller L. Drugs and grapefruit juice. Clin Pharmacol Ther. 1998; 63:87. http://www.ncbi.nlm.nih.gov/pubmed/9465845?dopt=AbstractPlus

66. Spence JD. Drugs and grapefruit juice. Clin Pharmacol Ther. 1998; 63:87-8. http://www.ncbi.nlm.nih.gov/pubmed/9465845?dopt=AbstractPlus

67. Bailey DG, Arnold MO, Munoz C et al. Grapefruit juice—felodipine interaction: mechanism, predictability, and effect of naringin. Clin Pharmacol Ther. 1993; 53:637-42. http://www.ncbi.nlm.nih.gov/pubmed/8513655?dopt=AbstractPlus

68. Manufacturer’s comments (Astra Merck, Wayne, PA): Personal communication.

69. Bailey DG, Arnold JMO, Spence JD. Grapefruit juice and drugs: how significant is the interaction? Clin Pharmacokinet. 1994; 26:91-8.

71. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. http://www.ncbi.nlm.nih.gov/pubmed/10818056?dopt=AbstractPlus

72. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. http://www.ncbi.nlm.nih.gov/pubmed/10818055?dopt=AbstractPlus

73. Bakris GL, Williams M, Dworkin L et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000; 36:646-61. http://www.ncbi.nlm.nih.gov/pubmed/10977801?dopt=AbstractPlus

74. Associated Press (American Diabetes Association). Diabetics urged: drop blood pressure. Chicago, IL; 2000 Aug 29. Press Release from web site. http://www.diabetes.org/newsroom/

75. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-60. http://www.ncbi.nlm.nih.gov/pubmed/12479770?dopt=AbstractPlus

76. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288:2981-97. http://www.ncbi.nlm.nih.gov/pubmed/12479763?dopt=AbstractPlus

81. Wright JT, Dunn JK, Cutler JA et al. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. JAMA. 2005; 293:1595-607. http://www.ncbi.nlm.nih.gov/pubmed/15811979?dopt=AbstractPlus

82. Neaton JD, Kuller LH. Diuretics are color blind. JAMA. 2005; 293:1663-6. http://www.ncbi.nlm.nih.gov/pubmed/15811986?dopt=AbstractPlus

83. Leenen FHH, Nwachuku CE, Black HR et al. Clinical events in high-risk hypertensive patients randomly assigned to calcium-channel blocker versus angiotensin-converting enzyme inhibitor in the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial. Hypertension. 2006; 48:374-84. http://www.ncbi.nlm.nih.gov/pubmed/16864749?dopt=AbstractPlus

84. Messerli FH, Staessen JA. Amlodipine better than lisinopril: how one randomized clinical trial ended fallacies from observational studies? Hypertension. 2006; 48:359-61. Editorial.

c. AHFS drug information 2004. McEvoy GK, ed. Nifedipine. Bethesda, MD: American Society of Health-System Pharmacists; 2004:1807-8.

501. 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; 311:507-20. http://www.ncbi.nlm.nih.gov/pubmed/24352797?dopt=AbstractPlus

502. Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013; 31:1281-357. http://www.ncbi.nlm.nih.gov/pubmed/23817082?dopt=AbstractPlus

503. Go AS, Bauman MA, Coleman 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. Hypertension. 2014; 63:878-85. http://www.ncbi.nlm.nih.gov/pubmed/24243703?dopt=AbstractPlus

504. 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; 16:14-26. http://www.ncbi.nlm.nih.gov/pubmed/24341872?dopt=AbstractPlus

505. Wright JT, Fine LJ, Lackland DT et al. Evidence supporting a systolic blood pressure goal of less than 150 mm Hg in patients aged 60 years or older: the minority view. Ann Intern Med. 2014; 160:499-503. http://www.ncbi.nlm.nih.gov/pubmed/24424788?dopt=AbstractPlus

506. Mitka M. Groups spar over new hypertension guidelines. JAMA. 2014; 311:663-4. http://www.ncbi.nlm.nih.gov/pubmed/24549531?dopt=AbstractPlus

507. Peterson ED, Gaziano JM, Greenland P. Recommendations for treating hypertension: what are the right goals and purposes?. JAMA. 2014; 311:474-6. http://www.ncbi.nlm.nih.gov/pubmed/24352710?dopt=AbstractPlus

508. Bauchner H, Fontanarosa PB, Golub RM. Updated guidelines for management of high blood pressure: recommendations, review, and responsibility. JAMA. 2014; 311:477-8. http://www.ncbi.nlm.nih.gov/pubmed/24352759?dopt=AbstractPlus

510. Staessen JA, Fagard R, Thijs L et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet. 1997; 350:757-64. http://www.ncbi.nlm.nih.gov/pubmed/9297994?dopt=AbstractPlus

511. JATOS Study Group. Principal results of the Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS). Hypertens Res. 2008; 31:2115-27. http://www.ncbi.nlm.nih.gov/pubmed/19139601?dopt=AbstractPlus

515. Thomas G, Shishehbor M, Brill D et al. New hypertension guidelines: one size fits most?. Cleve Clin J Med. 2014; 81:178-88. http://www.ncbi.nlm.nih.gov/pubmed/24591473?dopt=AbstractPlus

516. Wright JT, Bakris G, Greene T et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA. 2002; 288:2421-31. http://www.ncbi.nlm.nih.gov/pubmed/12435255?dopt=AbstractPlus

522. Patel A, ADVANCE Collaborative Group, MacMahon S et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007; 370:829-40. http://www.ncbi.nlm.nih.gov/pubmed/17765963?dopt=AbstractPlus

523. 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:e354-471.

524. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M et al. 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:e240-327.

525. Smith SC, Benjamin EJ, Bonow RO et al. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011; 124:2458-73. http://www.ncbi.nlm.nih.gov/pubmed/22052934?dopt=AbstractPlus

526. Kernan WN, Ovbiagele B, Black HR et al. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014; :. http://www.ncbi.nlm.nih.gov/pubmed/24788967?dopt=AbstractPlus

527. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013; 127:e362-425. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3695607&blobtype=pdf

530. Myers MG, Tobe SW. A Canadian perspective on the Eighth Joint National Committee (JNC 8) hypertension guidelines. J Clin Hypertens (Greenwich). 2014; 16:246-8. http://www.ncbi.nlm.nih.gov/pubmed/24641124?dopt=AbstractPlus

535. Taler SJ, Agarwal R, Bakris GL et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for management of blood pressure in CKD. Am J Kidney Dis. 2013; 62:201-13. http://www.ncbi.nlm.nih.gov/pubmed/23684145?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3929429&blobtype=pdf

536. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012: 2: 337-414.

541. Perk J, De Backer G, Gohlke H et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012; 33:1635-701. http://www.ncbi.nlm.nih.gov/pubmed/22555213?dopt=AbstractPlus

1150. 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 http://www.ncbi.nlm.nih.gov/pubmed/28827377?dopt=AbstractPlus

1200. 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. Hypertension. 2018; 71:el13-e115. http://www.ncbi.nlm.nih.gov/pubmed/29133356?dopt=AbstractPlus

1201. Bakris G, Sorrentino M. Redefining hypertension - assessing the new blood-pressure guidelines. N Engl J Med. 2018; 378:497-499. http://www.ncbi.nlm.nih.gov/pubmed/29341841?dopt=AbstractPlus

1202. Carey RM, Whelton PK, 2017 ACC/AHA Hypertension Guideline Writing Committee. Prevention, detection, evaluation, and management of high blood pressure in adults: synopsis of the 2017 American College of Cardiology/American Heart Association hypertension guideline. Ann Intern Med. 2018; 168:351-358. http://www.ncbi.nlm.nih.gov/pubmed/29357392?dopt=AbstractPlus

1207. Burnier M, Oparil S, Narkiewicz K et al. New 2017 American Heart Association and American College of Cardiology guideline for hypertension in the adults: major paradigm shifts, but will they help to fight against the hypertension disease burden?. Blood Press. 2018; 27:62-65. http://www.ncbi.nlm.nih.gov/pubmed/29447001?dopt=AbstractPlus

1209. Qaseem A, Wilt TJ, Rich R et al. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017; 166:430-437. http://www.ncbi.nlm.nih.gov/pubmed/28135725?dopt=AbstractPlus

1210. SPRINT Research Group, Wright JT, Williamson JD et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015; 373:2103-16. http://www.ncbi.nlm.nih.gov/pubmed/26551272?dopt=AbstractPlus

1213. Reboussin DM, Allen NB, Griswold ME et al. Systematic review for the 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. J Am Coll Cardiol. 2017; http://www.ncbi.nlm.nih.gov/pubmed/29146534?dopt=AbstractPlus

1216. Taler SJ. Initial treatment of hypertension. N Engl J Med. 2018; 378:636-644. http://www.ncbi.nlm.nih.gov/pubmed/29443671?dopt=AbstractPlus

1220. Cifu AS, Davis AM. Prevention, detection, evaluation, and management of high blood pressure in adults. JAMA. 2017; 318:2132-2134. http://www.ncbi.nlm.nih.gov/pubmed/29159416?dopt=AbstractPlus

1222. Bell KJL, Doust J, Glasziou P. Incremental benefits and harms of the 2017 American College of Cardiology/American Heart Association high blood pressure guideline. JAMA Intern Med. 2018; 178:755-7. http://www.ncbi.nlm.nih.gov/pubmed/29710197?dopt=AbstractPlus

1223. LeFevre M. ACC/AHA hypertension guideline: what is new? what do we do?. Am Fam Physician. 2018; 97(6):372-3. http://www.ncbi.nlm.nih.gov/pubmed/29671534%20?dopt=AbstractPlus

1224. Brett AS. New hypertension guideline is released. From NEJM Journal Watch website. Accessed 2018 Jun 18. https://www.jwatch.org/na45778/2017/12/28/nejm-journal-watch-general-medicine-year-review-2017

1229. Ioannidis JPA. Diagnosis and treatment of hypertension in the 2017 ACC/AHA guidelines and in the real world. JAMA. 2018; 319(2):115-6. http://www.ncbi.nlm.nih.gov/pubmed/29242891?dopt=AbstractPlus

1250. Weir MR, Josselson J, Giard MJ et al. Sustained-release diltiazem compared with atenolol monotherapy for mild to moderate systemic hypertension. Am J Cardiol. 1987; 60:36-41I. http://www.ncbi.nlm.nih.gov/pubmed/3604943?dopt=AbstractPlus

1251. Muller FB, Bolli P, Erne P et al. Use of calcium antagonists as monotherapy in the management of hypertension. Am J Med. 1984; 77(Suppl 2B):11-5. http://www.ncbi.nlm.nih.gov/pubmed/6385691?dopt=AbstractPlus

1252. Kiowski W, Bühler FR, Fadayomi MO et al. Age, race, blood pressure and renin: predictors for antihypertensive treatment with calcium antagonists. Am J Cardiol. 1985; 56:81-5H.

1253. Frishman WH, Charlap S, Michelson EL. Calcium channel blockers in systemic hypertension. Am J Cardiol. 1986; 58:157-60. http://www.ncbi.nlm.nih.gov/pubmed/3524178?dopt=AbstractPlus

1254. Halperin AK, Cubeddu LX. The role of calcium channel blockers in the treatment of hypertension. Am Heart J. 1986; 111:363-82. http://www.ncbi.nlm.nih.gov/pubmed/3511651?dopt=AbstractPlus

1255. Laragh JH. Issues, goals, and guidelines in selecting first-line drug therapy for hypertension. In: The National Heart, Lung, and Blood Institute workshop on antihypertensive drug treatment. Bethesda, MD; June 11–12, 1987. Hypertension. 1989; 13(Suppl I):I-103-12. http://www.ncbi.nlm.nih.gov/pubmed/2490815?dopt=AbstractPlus

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