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Nisoldipine (Monograph)

Brand name: Sular
Drug class: Dihydropyridines
- Calcium-Channel Blocking Agents, Dihydropyridine
- Calcium Antagonists
VA class: CV200
Chemical name: Methyl 2-methylpropyl ester 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid
Molecular formula: C20H24N2O6
CAS number: 63675-72-9

Medically reviewed by Drugs.com on Mar 11, 2024. Written by ASHP.

Introduction

Calcium-channel blocking agent; dihydropyridine derivative.1 2 3 4 5 6 8 9 10 11 12 42 45

Uses for Nisoldipine

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 11 12 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 have 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)45 523 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;80 81 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

Should not be used for acute management of hypertensive crises† [off-label].46

Nisoldipine Dosage and Administration

General

BP Monitoring and Treatment Goals

Administration

Oral Administration

Administer orally1 2 3 5 6 7 8 11 12 42 on an empty stomach (1 hour before or 2 hours after a meal);600 avoid concomitant administration with high-fat food.42 600

Extended-release tablets should be swallowed intact and should not be chewed, broken, or crushed.600

Dosage

Reformulated extended-release tablets containing 8.5 or 34 mg of nisoldipine are bioequivalent to original extended-release formulation (no longer commercially available) containing 10 or 40 mg, respectively.84

Adults

Hypertension
Extended-release Tablets
Oral

Manufacturer recommends initial dosage of 17 mg once daily.600

Increase as tolerated in increments of 8.5 mg daily at weekly or less frequent intervals up to 34 mg once daily.600 Monitor BP carefully during initial titration or subsequent upward adjustment in dosage.600

Usual maintenance dosage:17–34 mg once daily.600 1200

Prescribing Limits

Adults

Hypertension
Oral

Maximum 34 mg daily.600

Special Populations

Hepatic Impairment

Initially, 8.5 mg daily; monitor BP response closely with each dosage adjustment.600

Reduce initial and maintenance dosages in patients with cirrhosis.1

Renal Impairment

Dosage modification not necessary in patients with mild to moderate renal impairment.1

Geriatric Patients

Initially, 8.5 mg daily; monitor BP response closely with each dosage adjustment.600

Detailed Nisoldipine dosage information

Cautions for Nisoldipine

Contraindications

Warnings/Precautions

Warnings

Increased Angina and/or Acute MI

Rarely, increased frequency, duration, and/or severity of angina or acute MI, particularly in patients with severe obstructive CAD, upon initiation or dosage increase of calcium-channel blockers.1

Sensitivity Reactions

Tartrazine Sensitivity

Some preparations may contain tartrazine (FD&C yellow No. 5), which may cause allergic reactions including bronchial asthma in susceptible individuals.600 Incidence of tartrazine sensitivity is low, but it frequently occurs in patients who are sensitive to aspirin.600

General Precautions

Hypotension

Risk of excessive, poorly tolerated hypotension; usually occurs during initial dosage titration or subsequent upward titration.1 Carefully monitor BP, especially during therapy initiation, titration, or dosage increase; closely observe patients currently receiving drugs known to lower BP.1

Heart Failure

Use with caution in patients with heart failure or compromised ventricular function, especially in those receiving concomitant β-adrenergic blocking agents.1

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether nisoldipine is distributed into milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established.1

Geriatric Use

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

Hepatic Impairment

Use with caution in patients with severe hepatic impairment.1 Dosage reduction required.1 (See Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

Peripheral edema, headache, dizziness, pharyngitis, vasodilation, sinusitis, palpitation, chest pain, nausea, rash.1

Drug Interactions

Drugs Affecting Hepatic Microsomal Enzymes

Inducers of CYP3A4: Decreased plasma nisoldipine concentrations.1 601 Generally avoid concomitant use.600 601

Inhibitors of CYP3A4: Increased plasma nisoldipine concentrations.600 Generally avoid concomitant use.600

Specific Drugs and Foods

Drug or Food

Interaction

Comments

β-Adrenergic blocking agents

Increased risk of hypotension and exacerbation of heart failure1

Digoxin

Pharmacokinetic interaction unlikely1

Grapefruit juice

Increased nisoldipine bioavailability1

Avoid grapefruit-containing foods and beverages for at least 1 hour before and after administration of a dose1 44 46

Histamine H2-receptor antagonists

Possible increased nisoldipine concentrations with cimetidine; no significant interaction with ranitidine1

Phenytoin

Decreased plasma concentrations of nisoldipine to undetectable levels1

Avoid concomitant use1

Quinidine

Possible decreased AUC of nisoldipine1

Clinical significance unknown1

Warfarin

Pharmacokinetic interaction unlikely1
Nisoldipine drug interactions (more detail)

Nisoldipine Pharmacokinetics

Absorption

Bioavailability

Relatively well absorbed from the GI tract following oral administration,600 601 with peak plasma concentrations attained in about 9.2 hours.600

Absolute bioavailability is low (about 5%), due to presystemic metabolism in the intestine; presystemic metabolism decreases from proximal to distal parts of intestine.1 600 601 602 Bioavailability of extended-release preparation is increased since nisoldipine is released in the colon where presystemic metabolism is reduced.1 601 602

Food

A high-fat meal increases peak plasma concentrations by up to 245%, but decreases AUC by 25%.600

Special Populations

In geriatric patients, plasma concentrations increased about 2- to 3-fold.1

In patients with hepatic cirrhosis, plasma concentrations increased by 4–5 times.1

Distribution

Extent

Not known whether nisoldipine is distributed into milk.1

Plasma Protein Binding

>99%.1 601

Elimination

Metabolism

Extensively metabolized; major pathway appears to involve hydroxylation.600 Thought to be metabolized principally by CYP isoenzymes.1 Precise enzymes responsible for metabolism are unknown, but other dihydropyridine-derivative calcium-channel blocking agents are metabolized by CYP3A4.1

Elimination Route

Excreted principally in urine (60–80%) as metabolites.1

Half-life

Approximately 13.7 hours.600

Stability

Storage

Oral

Extended-Release Tablets

Tight, light-resistant containers at 20–25°C.1 Protect from light and moisture.1

Actions

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

Nisoldipine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release, film-coated

8.5 mg*

Nisoldipine Extended-release Tablets

Sular

Shionogi

17 mg*

Nisoldipine Extended-release Tablets

Sular

Shionogi

25.5 mg*

Nisoldipine Extended-release Tablets

34 mg*

Nisoldipine Extended-release Tablets

Sular

Shionogi

AHFS DI Essentials™. © Copyright 2024, Selected Revisions March 19, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

References

1. First Horizon.Sular (nisoldipine) extended-release tablets prescribing information. (dated 2004 Mar). In: Physicians' desk reference. From the PDR electronic library website. Accessed 2006 Nov 9. http://pdrel.thomsonhc.com

2. Zannad F. Clinical pharmacology of nisoldipine coat core. Am J Cardiol. 1995; 75:41-5E.

3. Mitchell J, Frishman W, Heiman M. Nisoldipine: a new dihydropyridine calcium-channel blocker. J Clin Pharmacol. 1993; 33:46-52. http://www.ncbi.nlm.nih.gov/pubmed/8429113?dopt=AbstractPlus

4. Knorr AM. Why is nisoldipine a specific agent in ischemic left ventricular dysfunction? Am J Cardiol. 1995; 75:36-40E.

5. Fujii Y, Hattori S, Nagami K et al. The hypotensive effect of nisoldipine: 24-hour blood pressure profile and serial alterations of renal and hormonal function. Curr Ther Res. 1994; 55:93-101.

6. Ishiguro M, Shimabukuro S, Minagawa T et al. Evaluation of nisoldipine by noninvasive ambulatory blood pressure monitoring in patients with hypertension. Curr Ther Res. 1991; 50:804-11.

7. Nakanishi T, Takahashi H, Yoshimura M et al. Effects of nisoldipine on ambulatory blood pressure in patients with essential hypertension. Curr Ther Res. 1991; 50:417-24.

8. Shionoiri H, Sugiyama K, Takasaki I et al. Antihypertensive effects of nisoldipine in patients with essential hypertension. Curr Ther Res. 1989; 45:253-61.

9. Lewis BS. Efficacy and safety of nisoldipine coat core in the management of angina pectoris, systemic hypertension, and ischemic ventricular dysfunction. Am J Cardiol. 1995; 75:46E-53E. http://www.ncbi.nlm.nih.gov/pubmed/7726125?dopt=AbstractPlus

10. Glasser SP. Nisoldipine coat core as concomitant therapy in chronic stable angina pectoris. Am J Cardiol. 1995; 75:68-70E.

11. Shaw-Stiffel TA, Walker SE, Ogilvie RI et al. Pharmacokinetic and pharmacodynamic interactions during multiple-dose administration of nisoldipine and propranolol. Clin Pharmacol Ther. 1994; 55:661-9. http://www.ncbi.nlm.nih.gov/pubmed/8004882?dopt=AbstractPlus

12. Rosenfeld JB, Zabludowski J. The efficacy and tolerability of nifedipine (NIF) and nisoldipine (NIS) both alone and combined with a beta-blocker in patients with essential hypertension: a multicenter, parallel-group study. J Clin Pharmacol. 1989; 29:1013-16. http://www.ncbi.nlm.nih.gov/pubmed/2574728?dopt=AbstractPlus

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

15. 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

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

17. 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.

18. 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.

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

20. 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

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

22. 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

23. 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

24. 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

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

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

27. 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

28. 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

29. 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

30. 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

31. 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

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

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

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

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

36. 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

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

38. 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

39. Reviewers’ comments (personal observations) on Nifedipine 24:28.

40. 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.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1838102&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/2513047?dopt=AbstractPlus

41. 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

42. Anon. Nisoldipine—a new calcium channel blocker for hypertension. Med Lett Drugs Ther. 1996; 38:13-4. http://www.ncbi.nlm.nih.gov/pubmed/8592476?dopt=AbstractPlus

43. Anon. grapefruit juice interactions with drugs. Med Lett Drugs Ther. 1995; 37:73-4. http://www.ncbi.nlm.nih.gov/pubmed/7630329?dopt=AbstractPlus

44. Bailey DG, Arnold JMO, Strong HA et al. Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics. Clin Pharmacol Ther. 1993; 54:589-94. http://www.ncbi.nlm.nih.gov/pubmed/8275614?dopt=AbstractPlus

45. Kaplan NM, Gifford RW. Choice of initial therapy for hypertension. JAMA. 1996; 275:1577-9. http://www.ncbi.nlm.nih.gov/pubmed/8622249?dopt=AbstractPlus

46. Zeneca Pharmaceuticals, Wilmington, DE: Personal communication.

47. Chandler MHH, Clifton GD, Lettieri JT et al. Multiple dose pharmacokinetics of four different doses of nisoldipine in hypertensive patients. J Clin Pharmacol. 1992; 32:571-5. http://www.ncbi.nlm.nih.gov/pubmed/1634646?dopt=AbstractPlus

48. Marazzi P. A study to demonstrate the equivalence in efficacy and safety of once-daily nisoldipine CC and amlodipine in the treatment of mild to moderate hypertension. Acta Ther. 1996; 22:23-35.

49. Lasseter KC, Muller FO, Garrett BN et al. Pharmacokinetics, pharmacodynamics, and clinical utility of nisoldipine coat core in the treatment of essential hypertension. Cardiovasc Rev Rep. 1996; 17:28,31-35,38,44-46.

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

52. 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

53. American College of Cardiology and American Heart Association. ACC/AHA guidelines for the management of patients with acute myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). J Am Coll Cardiol. 1996; 28:1328-428. http://www.ncbi.nlm.nih.gov/pubmed/8890834?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. 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

65. Reviewers’ comments (personal observations).

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

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

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

69. 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

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

71. 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

72. 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/

73. 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

74. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-riskhypertensive 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

79. Carter B for the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Personal communication.

80. 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

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

82. 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

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

84. US Food and Drug Administration. Center for Drug Evaluation and Research. Approval package for application number 20-356/S-019. From FDA website. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/020356Orig1s019.pdf

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.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3929429&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/23684145?dopt=AbstractPlus

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

600. Shionogi. Sular (nisoldipine) film-coated, extended-release tablets prescribing information. Florham Park, NJ; 2014 Mar

601. Heinig R. Clinical pharmacokinetics of nisoldipine coat-core. Clin Pharmacokinet. 1998; 35:191-208. http://www.ncbi.nlm.nih.gov/pubmed/9784933?dopt=AbstractPlus

602. Heinig R. Ahr G, Hayauchi Y et al. Pharmacokinetics of the controlled-release nisoldipine coat-core tablet formulation. Int J Clin Pharmacol. 1997; 35:341-51.

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?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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