amLODIPine (Monograph)

Brand name: Norvasc
Drug class: Dihydropyridines
- Calcium-Channel Blocking Agents, Dihydropyridine
- Dihydropyridine Calcium-Channel Blocking Agents
- Calcium Antagonists
VA class: CV200
CAS number: 111470-99-6

Medically reviewed by Drugs.com on Oct 11, 2023. Written by ASHP.

Introduction

Amlodipine is a calcium-channel blocking agent; a dihydropyridine derivative with an intrinsically long duration of action.¹ ² ³

Uses for amLODIPine

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents);¹ ² ³ ⁴ ⁵ ⁶ ²¹ ¹¹³ ¹²⁹ ¹³⁰ ¹³² ¹³³ ¹³⁴ ¹²⁰⁰ may be used in fixed combination with benazepril, olmesartan, olmesartan and hydrochlorothiazide, perindopril, telmisartan, valsartan, or valsartan and hydrochlorothiazide when such combined therapy is indicated.²¹ ¹¹³ ¹²⁹ ¹³⁰ ¹³² ¹³³ ¹³⁴

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) <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 generally 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

Previous 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 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 current 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 current ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.¹²⁰⁰ ¹²⁰⁷ ASCVD risk assessment 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 patients 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 of age 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 preferred 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

Black hypertensive 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).⁶⁹ ⁷⁰ ⁹⁵ ¹⁰⁸ ¹⁰⁹ ⁵⁰¹ ⁵⁰⁴ 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

Amlodipine should not be used for acute management of hypertensive crises.¹

Addition of an ACE inhibitor or angiotensin II receptor antagonist may reduce incidence of amlodipine-associated edema.²¹ ¹³⁴ ⁵⁰⁴

May use amlodipine/atorvastatin fixed-combination preparation when treatment with both amlodipine (for hypertension) and atorvastatin (for dyslipidemias and prevention of cardiovascular events) is appropriate.¹⁰⁷

CAD

Amlodipine is used for management of Prinzmetal variant angina and chronic stable angina pectoris;¹ ² ³ ⁴ ⁹ has been used alone or in combination with other antianginal agents.¹ ² ³ ⁴ ⁹ Calcium-channel blockers are considered the drugs of choice in management of Prinzmetal variant angina.^b

Amlodipine is used in patients with recently documented CAD (by angiography) and without heart failure or an ejection fraction <40% to reduce the risk of coronary revascularization procedure and hospitalization due to angina.¹

May use amlodipine/atorvastatin fixed-combination preparation when treatment with both amlodipine (for CAD) and atorvastatin (for dyslipidemias and prevention of cardiovascular events) is appropriate.¹⁰⁷

amLODIPine 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.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

Administration

Oral Administration

Administer amlodipine orally without regard to meals.¹ ² ³ ⁵

Dosage

Available as amlodipine besylate; dosage expressed in terms of amlodipine.¹

Pediatric Patients

Hypertension

Amlodipine Therapy

Oral

Initiate drug at the low end of the dosage range per some experts; may increase dosage every 2–4 weeks until BP controlled, maximum dosage reached, or adverse effects occur.¹¹⁵⁰

Children 1–5 years of age^{† [off-label]}: Some experts recommend an initial dosage of 0.1 mg/kg once daily and a maximum dosage 0.6 mg/kg once daily (up to 5 mg daily).¹¹⁵⁰

Children ≥6 years of age: Some experts recommend an initial dosage of 2.5 mg once daily and a maximum dosage of 10 mg once daily.¹¹⁵⁰ However, manufacturer states safety and efficacy of dosages >5 mg daily not established in pediatric patients.¹¹⁵⁰ Manufacturer states usual effective amlodipine dosage is 2.5–5 mg once daily.¹

Adults

Hypertension

Amlodipine

Oral

Manufacturers state usual initial dosage is 2.5–5 mg once daily.¹ In small or frail individuals, initiate therapy with 2.5 mg once daily.¹

When adding amlodipine to an existing antihypertensive regimen, use initial dosage of 2.5 mg once daily.¹

Increase amlodipine dosage gradually, generally at 7- to 14-day intervals, until optimum control of BP is obtained (up to a maximum dosage of 10 mg daily).¹ May increase more rapidly if symptoms so warrant and patient’s tolerance and response are frequently assessed.¹

Usual maintenance dosage is 2.5–10 mg once daily.¹ ¹²⁰⁰

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

Amlodipine/Benazepril Fixed-combination

Oral

Manufacturers state that amlodipine/benazepril fixed-combination preparation usually should be used only after therapy with either drug component alone has failed.²¹

In studies using amlodipine/benazepril fixed combination in dosages of amlodipine 2.5–10 mg daily and benazepril hydrochloride 10–40 mg daily, BP response increased with increasing amlodipine dosage in all patient groups and increased with increasing benazepril dosage in nonblack patient groups.²¹

If BP is not adequately controlled by monotherapy with amlodipine (or another dihydropyridine-derivative calcium-channel blocker) or benazepril (or another ACE inhibitor), can switch to amlodipine/benazepril fixed combination.²¹

If BP is adequately controlled by monotherapy with amlodipine, but edema has developed, can switch to amlodipine/benazepril fixed combination.²¹ Addition of benazepril to amlodipine therapy usually does not provide additional antihypertensive effects in black patients, but benazepril appears to reduce the development of amlodipine-associated edema regardless of race.²¹

If BP is controlled with amlodipine and benazepril (administered separately), can switch to the fixed-combination preparation containing the corresponding individual doses for convenience.²¹

Recommended initial dosage is amlodipine 2.5 mg and benazepril hydrochloride 10 mg once daily.²¹

Adjust dosage of amlodipine/benazepril fixed combination according to patient’s response, up to maximum of amlodipine 10 mg and benazepril hydrochloride 40 mg once daily; antihypertensive effect of a given dosage is largely attained with 2 weeks.²¹

Amlodipine/Olmesartan Fixed-combination

Oral

Fixed-combination amlodipine/olmesartan tablets may be used for initial treatment of hypertension in patients likely to require combination therapy with multiple antihypertensive agents to control BP.¹³⁴

If the patient’s baseline BP is 160/100 mm Hg, the estimated probability of achieving SBP control (SBP <140 mm Hg) is 48, 46, or 68% and of achieving DBP control (DBP <90 mm Hg) is 51, 60, or 85% with olmesartan medoxomil (40 mg daily) alone, amlodipine (10 mg daily) alone, or amlodipine combined with olmesartan medoxomil (same dosages), respectively.¹³⁴

If BP is not adequately controlled by monotherapy with amlodipine (or another dihydropyridine-derivative calcium-channel blocker) or olmesartan (or another angiotensin II receptor antagonist), can switch to amlodipine/olmesartan fixed combination.¹³⁴

Can use the fixed combination as a substitute for the individually titrated drugs.¹³⁴ Can switch to the fixed-combination preparation containing the corresponding individual doses of amlodipine and olmesartan; alternatively, can increase the dosage of one or both components for additional antihypertensive effects.¹³⁴

Adjust dosage of amlodipine/olmesartan fixed combination, up to a maximum of amlodipine 10 mg and olmesartan medoxomil 40 mg once daily, according to patient’s response after ≥2 weeks at the current dosage.¹³⁴

When used for initial therapy of hypertension in patients likely to require combination therapy with multiple antihypertensive agents, recommended initial dosage is amlodipine 5 mg and olmesartan medoxomil 20 mg once daily.¹³⁴ May increase dosage after 1–2 weeks for additional BP control, up to maximum of amlodipine 10 mg and olmesartan medoxomil 40 mg once daily.¹³⁴

Amlodipine/Olmesartan/Hydrochlorothiazide Fixed-combination

Oral

Manufacturer states that amlodipine/olmesartan/hydrochlorothiazide fixed-combination preparation should not be used for initial treatment of hypertension.¹³²

Can switch to fixed-combination amlodipine/olmesartan/hydrochlorothiazide tablets if BP is not adequately controlled by combined therapy with any 2 of the following drug classes at maximally tolerated, labeled, or usual dosages: calcium-channel blockers, angiotensin II receptor antagonists, or diuretics.¹³²

In patients who experience dose-limiting adverse effects of olmesartan, amlodipine, or hydrochlorothiazide while receiving any dual combination of these drugs, may switch to the triple fixed-combination preparation containing a lower dose of that component.¹³²

Can use the fixed combination as a substitute for the individually titrated drugs.¹³²

May increase dosage of the fixed combination after 2 weeks if additional BP control is needed (up to maximum of amlodipine 10 mg, olmesartan medoxomil 40 mg, and hydrochlorothiazide 25 mg once daily).¹³²

Amlodipine/Perindopril Fixed-combination

Oral

Fixed-combination amlodipine/perindopril tablets may be used for initial treatment of hypertension in patients likely to require combination therapy with multiple antihypertensive agents to control BP.¹³⁰ Consider potential benefits and risks of initiating therapy with the fixed combination, including whether the patient is likely to tolerate the lowest available dosage of the combined drugs.¹³⁰

If patient’s baseline BP is 170/105 mm Hg, the estimated probability of achieving SBP control (SBP <140 mm Hg) is 26, 40, or 50% and of achieving DBP control (DBP <90 mm Hg) is 31, 46, or 65% with perindopril erbumine (16 mg daily) alone, amlodipine (10 mg daily) alone, or amlodipine (10 mg daily) combined with perindopril arginine (14 mg daily), respectively.¹³⁰

If BP is not adequately controlled by monotherapy with amlodipine (or another dihydropyridine-derivative calcium-channel blocker) or perindopril (or another ACE inhibitor), can switch to amlodipine/perindopril fixed combination.¹³⁰

In black patients and patients with diabetes mellitus, addition of perindopril arginine (14 mg daily) to amlodipine (10 mg daily) did not provide additional antihypertensive effects beyond those achieved with amlodipine monotherapy.¹³⁰

If BP is adequately controlled by monotherapy with amlodipine, but edema has developed, can switch to amlodipine/perindopril fixed combination to achieve BP control without edema.¹³⁰

May adjust dosage at intervals of 7–14 days, up to maximum of amlodipine 10 mg and perindopril arginine 14 mg once daily.¹³⁰

Amlodipine/Telmisartan Fixed-combination

Oral

Fixed-combination amlodipine/telmisartan tablets may be used for initial treatment of hypertension in patients likely to require combination therapy with multiple antihypertensive agents to control BP.¹²⁹ Consider potential benefits and risks of initiating therapy with the fixed combination, including whether the patient is likely to tolerate the lowest available dosage of the combined drugs.¹²⁹

If the patient’s baseline BP is 160/110 mm Hg, the estimated probability of achieving SBP control (SBP <140 mm Hg) is 46, 69, or 79% and of achieving DBP control (DBP <90 mm Hg) is 26, 22, or 55% with telmisartan (80 mg daily) alone, amlodipine (10 mg daily) alone, or amlodipine combined with telmisartan (same dosages), respectively.¹²⁹

If BP is not adequately controlled by monotherapy with amlodipine (or another dihydropyridine-derivative calcium-channel blocker) or telmisartan (or another angiotensin II receptor antagonist), can switch to amlodipine/telmisartan fixed combination.¹²⁹

If dose-limiting adverse effects (e.g., edema) have developed during monotherapy with amlodipine 10 mg, can switch to the fixed-combination preparation containing amlodipine 5 mg and telmisartan 40 mg to achieve similar BP control; adjust dosage according to patient’s response after ≥2 weeks of therapy.¹²⁹

Can use the fixed combination as a substitute for the individually administered drugs.¹²⁹ Can switch to the fixed-combination preparation containing the corresponding individual doses of amlodipine and telmisartan; alternatively, can increase the dosage of one or both components for additional antihypertensive effects.¹²⁹

When used for initial therapy of hypertension in patients likely to require combination therapy with multiple antihypertensive agents, usual initial dosage is amlodipine 5 mg and telmisartan 40 mg once daily; initial dosage of amlodipine 5 mg and telmisartan 80 mg once daily may be used in patients requiring larger BP reductions.¹²⁹

Increase to maximum dosage of amlodipine 10 mg and telmisartan 80 mg once daily, if needed, to control BP.¹²⁹ May adjust dosage at intervals of at least 2 weeks, since most of the antihypertensive effect of a given dosage is achieved within 2 weeks after a change in dosage.¹²⁹

Amlodipine/Valsartan Fixed-combination

Oral

Fixed-combination amlodipine/valsartan tablets may be used for initial treatment of hypertension in patients likely to require combination therapy with multiple antihypertensive agents to control BP.¹¹³ Consider potential benefits and risks of initiating therapy with the fixed combination, including whether the patient is likely to tolerate the lowest available dosage of the combined drugs.¹¹³

If the patient’s baseline BP is 160/100 mm Hg, the estimated probability of achieving SBP control (SBP <140 mm Hg) is 47, 67, or 80% and of achieving DBP control (DBP <90 mm Hg) is 62, 80, or 85% with valsartan (320 mg daily) alone, amlodipine (10 mg daily) alone, or amlodipine combined with valsartan (same dosages), respectively.¹¹³

In studies using amlodipine/valsartan fixed combination in dosages of amlodipine 5–10 mg daily and valsartan 160–320 mg daily, BP response increased with increasing dosages of the drugs.¹¹³

If BP is not adequately controlled by monotherapy with amlodipine (or another dihydropyridine-derivative calcium-channel blocker) or valsartan (or another angiotensin II receptor antagonist), can switch to amlodipine/valsartan fixed combination.¹¹³

If dose-limiting adverse effects have developed during monotherapy with amlodipine or valsartan, can switch to a fixed-combination preparation containing a lower dose of that drug to achieve similar BP control; adjust dosage according to patient’s response after 3–4 weeks of therapy.¹¹³

If BP is controlled with amlodipine and valsartan (administered separately), can switch to the fixed-combination preparation containing the corresponding individual doses for convenience.¹¹³

Increase to maximum dosage of amlodipine 10 mg and valsartan 320 mg once daily, if needed, to control BP.¹¹³ May adjust dosage at intervals of 1–2 weeks, since most of the antihypertensive effect of a given dosage is achieved within 2 weeks after a change in dosage.¹¹³

Amlodipine/Valsartan/Hydrochlorothiazide Fixed-combination

Oral

Manufacturers state amlodipine/valsartan/hydrochlorothiazide fixed-combination preparation should not be used for initial treatment of hypertension.¹³³

Can switch to fixed-combination amlodipine/valsartan/hydrochlorothiazide tablets if BP is not adequately controlled by combined therapy with any 2 of the following drug classes: calcium-channel blockers, angiotensin II receptor antagonists, or diuretics.¹³³

In patients who experience dose-limiting adverse effects of amlodipine, valsartan, or hydrochlorothiazide while receiving any dual combination of these drugs, may switch to the triple fixed-combination preparation containing a lower dose of that component.¹³³

Can use the fixed combination as a substitute for the individually titrated drugs.¹³³

May increase dosage of the fixed combination after 2 weeks if additional BP control is needed (up to maximum of amlodipine 10 mg, valsartan 320 mg, and hydrochlorothiazide 25 mg once daily).¹³³

Amlodipine/Atorvastatin Fixed-combination Therapy for Hypertension (Amlodipine) and for Dyslipidemias and Prevention of Cardiovascular Events (Atorvastatin)

Oral

Use the fixed combination as a substitute for the individually titrated drugs.¹⁰⁷ Can switch to the fixed-combination preparation containing the corresponding individual doses of amlodipine and atorvastatin; alternatively, can increase the dosage of one or both components for additional antihypertensive and/or antilipemic effects.¹⁰⁷

Use the fixed combination to provide additional therapy for patients currently receiving one component of the preparation.¹⁰⁷ Select initial dosage of the fixed combination based on the current dosage of the component being used and the recommended initial dosage for the added monotherapy.¹⁰⁷

Use the fixed combination to initiate treatment in patients requiring therapy for hypertension and dyslipidemias.¹⁰⁷ Select initial dosage of the fixed combination based on recommended dosages of the individual components.¹⁰⁷

CAD

Amlodipine Therapy for Angina

Oral

Usual amlodipine dosage is 5–10 mg once daily;¹ ² adequate control usually requires a maintenance dosage of 10 mg daily.¹

Amlodipine Therapy for Angiographically Documented CAD

Oral

Recommended amlodipine dosage is 5–10 mg once daily;¹ adequate control usually requires a maintenance dosage of 10 mg daily.¹

Amlodipine/Atorvastatin Fixed-combination Therapy for CAD (Amlodipine) and for Dyslipidemias and Prevention of Cardiovascular Events (Atorvastatin)

Oral

Use the fixed combination to initiate treatment in patients requiring therapy for angina and dyslipidemias.¹⁰⁷ Select initial dosage of the fixed combination based on recommended dosages of the individual components.¹⁰⁷

Prescribing Limits

Pediatric Patients

Hypertension

Oral

Children 1–5 years of age^{† [off-label]}: Some experts recommend maximum of 0.6 mg/kg (up to 5 mg) daily.¹¹⁵⁰

Children ≥6 years of age: Manufacturer states safety and efficacy of amlodipine dosages >5 mg daily not established.¹ Alternatively, some experts recommend maximum of 10 mg daily.¹¹⁵⁰

Adults

Hypertension

Oral

Maximum 10 mg of amlodipine once daily.¹ ¹⁰⁷ ¹¹³ ¹³⁴

Special Populations

The following information addresses dosage of amlodipine in special populations. Dosages of drugs administered in fixed combination with amlodipine also may require adjustment in certain patient populations; the need for such dosage adjustments must be considered in the context of cautions, precautions, and contraindications specific to that population and drug.²¹ ¹⁰⁷ ¹¹³ ¹³⁴

Hepatic Impairment

Hypertension

Initially, amlodipine 2.5 mg once daily (as initial or add-on therapy).¹ ²¹ ¹⁰⁷ ¹²⁹ ¹³⁴ Titrate slowly.¹ ¹³²

Amlodipine/perindopril fixed combination not recommended in patients with hepatic impairment; insufficient data to support dosage recommendations.¹³⁰

Preparations containing amlodipine in fixed combination with olmesartan (with or without hydrochlorothiazide), telmisartan, or valsartan (with or without hydrochlorothiazide) exceed recommended initial dosage of amlodipine (2.5 mg daily) for patients with hepatic insufficiency.¹¹³ ¹²⁹ ¹³² ¹³³ ¹³⁴

Angina

Initially, amlodipine 5 mg daily.¹ ¹⁰⁷

Renal Impairment

Amlodipine dosage modification generally not necessary.¹ ² ³ ⁵

Amlodipine/benazepril fixed combination not recommended in patients with Cl_cr ≤30 mL/minute.²¹

Amlodipine/olmesartan/hydrochlorothiazide fixed combination not recommended in patients with Cl_cr ≤30 mL/minute; loop diuretic generally preferred over hydrochlorothiazide.¹³²

Amlodipine/perindopril fixed combination not recommended in patients with Cl_cr <60 mL/minute; insufficient data to support dosage recommendations.¹³⁰

Safety and efficacy of preparations containing amlodipine in fixed combination with valsartan (with or without hydrochlorothiazide) in patients with Cl_cr <30 mL/minute not established.¹¹³ ¹³³

Manufacturers recommend slow titration of amlodipine/telmisartan dosage in patients with severe renal impairment.¹²⁹

Geriatric Patients

Hypertension

Consider reduced initial amlodipine dosage.¹ ² ⁴ ²¹ ¹⁰⁷ ¹¹³ ¹²⁹ ¹³² ¹³³ ¹³⁴ Some manufacturers recommend initial dosage of 2.5 mg once daily for geriatric patients;¹ others recommend this reduced dosage for geriatric patients ≥75 years of age.¹¹³ ¹²⁹ ¹³² ¹³⁴

Preparations containing amlodipine in fixed combination with olmesartan (with or without hydrochlorothiazide), telmisartan, or valsartan (with or without hydrochlorothiazide) exceed recommended initial dosage of amlodipine (2.5 mg daily) for geriatric patients.¹¹³ ¹²⁹ ¹³² ¹³³ ¹³⁴

Amlodipine/perindopril fixed combination not recommended; insufficient data available to support geriatric dosage recommendations.¹³⁰

Angina

Initially, amlodipine 5 mg daily.¹ ¹⁰⁷

Heart Failure

Manufacturers make no specific dosage recommendations; however, amlodipine exposure in patients with moderate to severe heart failure similar to that in geriatric patients and those with hepatic impairment.¹

Amlodipine/perindopril fixed combination not recommended in patients with heart failure; insufficient data to support dosage recommendations.¹³⁰

Cautions for amLODIPine

Contraindications

Known hypersensitivity to amlodipine.¹ ²¹ ¹⁰⁷

Warnings/Precautions

Hypotension

Possible symptomatic hypotension, particularly in patients with severe aortic stenosis.¹ Acute hypotension unlikely because of gradual onset of action.¹

Increased Angina and/or Acute MI

Possible worsening of angina or acute MI, particularly in patients with severe obstructive CAD, upon initiation or dosage increase of amlodipine.¹

Use of Fixed Combinations

When amlodipine is used in fixed combination with other drugs (e.g., other antihypertensive agents, atorvastatin), consider cautions, precautions, contraindications, and interactions associated with the concomitant agent(s).²¹ ¹⁰⁷ ¹¹³ ¹²⁹ ¹³⁰ ¹³² ¹³³ ¹³⁴ Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for each drug in the fixed combination.²¹ ¹⁰⁷ ¹¹³ ¹²⁹ ¹³⁰ ¹³² ¹³³ ¹³⁴

Heart Failure

Although some calcium-channel blockers have been shown to worsen clinical status of patients with heart failure, no evidence of worsening heart failure and no adverse effects on overall survival or cardiac morbidity observed in controlled studies of amlodipine in patients with heart failure.¹ ⁵²⁴

Specific Populations

Pregnancy

Category C.¹

Lactation

Not known whether amlodipine is distributed into milk; manufacturer recommends discontinuance of nursing if amlodipine is used.¹

Pediatric Use

Safety and efficacy of amlodipine in children <6 years of age not established.¹ Efficacy of amlodipine 2.5–5 mg daily for treatment of hypertension established in pediatric patients 6–17 years of age.¹

Safety and efficacy of amlodipine in fixed combination with atorvastatin, benazepril, olmesartan (with or without hydrochlorothiazide), perindopril, telmisartan, or valsartan (with or without hydrochlorothiazide) not established in children.²¹ ¹⁰⁷ ¹¹³ ¹²⁹ ¹³⁰ ¹³² ¹³³ ¹³⁴

Geriatric Use

Increased amlodipine exposure. ¹ Select amlodipine dosage with caution; initiate with dosage at lower end of recommended range.¹ ¹¹³ (See Geriatric Patients under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Amlodipine: Clinical studies included insufficient numbers of patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients; other clinical experience has not revealed age-related differences in response or tolerance.¹

Amlodipine in fixed combination with benazepril, olmesartan (with or without hydrochlorothiazide), telmisartan, or valsartan (with or without hydrochlorothiazide): No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.²¹ ¹¹³ ¹²⁹ ¹³² ¹³³ ¹³⁴

Amlodipine in fixed combination with perindopril: Safety and efficacy not established in geriatric patients.¹³⁰

Amlodipine in fixed combination with atorvastatin: Safety and efficacy not established in geriatric patients.¹⁰⁷

Hepatic Impairment

Increased amlodipine exposure.¹ Reduced initial dosage recommended;¹ ² ⁴ ²¹ ¹⁰⁷ ¹¹³ ¹²⁹ ¹³² ¹³³ ¹³⁴ titrate slowly.¹ ¹²⁹ (See Hepatic Impairment under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Common Adverse Effects

Edema, dizziness, flushing, palpitations, fatigue, nausea, abdominal pain, somnolence.¹ Edema, flushing, palpitations, and somnolence may be more common in women than men.¹ Edema may be less frequent with concomitant ACE inhibitor or angiotensin II receptor antagonist therapy.²¹ ¹³⁴ ⁵⁰⁴

Drug Interactions

The following information addresses potential interactions with amlodipine. When amlodipine is used in fixed combination with other drugs, consider interactions associated with the concomitant agent(s).²¹ ¹⁰⁷ ¹¹³ ¹²⁹ ¹³⁰ ¹³² ¹³³ ¹³⁴

Drugs Affecting Hepatic Microsomal Enzymes

Moderate or potent CYP3A inhibitors: Increased amlodipine exposure.¹ Amlodipine dosage reduction may be necessary.¹ Monitor patients for symptoms of hypotension or edema.¹

CYP3A inducers: Data lacking; closely monitor BP.¹

Specific Drugs and Food

Drug or Food	Interaction	Comments
Alcohol	No change in alcohol exposure¹
Antacids (e.g., aluminum hydroxide and magnesium hydroxide)	No change in amlodipine exposure¹
Antifungals, azole (e.g., itraconazole)	Possible increased amlodipine exposure¹	Amlodipine dosage reduction may be necessary; monitor patients for hypotension and edema¹
Cimetidine	No effects on amlodipine exposure¹
Digoxin	No effects on digoxin exposure¹ No change in plasma protein binding of digoxin¹
Diltiazem	Increased amlodipine exposure¹	Amlodipine dosage reduction may be necessary; monitor patients for hypotension and edema¹
HMG-CoA reductase inhibitors (statins)	Atorvastatin: No effects on atorvastatin exposure¹ Simvastatin: Increased simvastatin exposure¹	Simvastatin: Limit simvastatin dosage to ≤20 mg daily¹
Grapefruit juice	Altered amlodipine bioavailability possible but no evidence of altered pharmacodynamics;⁶⁴ ⁶⁵ ⁷⁴ ⁷⁵ no change in amlodipine exposure in another study¹
Immunosuppressants (cyclosporine, tacrolimus)	Cyclosporine: Increased cyclosporine trough concentrations¹ Tacrolimus: Increased tacrolimus exposure, possibly irrespective of CYP3A5 genotype¹	Frequently monitor blood concentrations of the immunosuppressant; adjust the immunosuppressant dosage as necessary¹
Indomethacin	No change in plasma protein binding of indomethacin¹
Macrolides (clarithromycin, erythromycin)	Clarithromycin: Possible increased amlodipine exposure¹ Erythromycin: No substantial change in amlodipine exposure¹	Clarithromycin: Amlodipine dosage reduction may be necessary; monitor patients for hypotension and edema¹
Phenytoin	No change in plasma protein binding of phenytoin¹
Sildenafil	Pharmacokinetic interaction unlikely; additional reduction of BP possible¹	Monitor patients for hypotension¹
Warfarin	No change in PT¹ No change in plasma protein binding of warfarin¹

amLODIPine Pharmacokinetics

Absorption

Bioavailability

Peak plasma amlodipine concentrations attained 6–12 hours after oral administration.¹ Absolute bioavailability ranges from 64–90%.¹

Duration

Antihypertensive effects of amlodipine persist for at least 24 hours after administration.¹

Food

Food does not affect bioavailability of amlodipine.¹ ¹⁰⁷ ¹¹³ ¹²⁹ ¹³⁰ ¹³² ¹³³ ¹³⁴

Distribution

Extent

Not known whether amlodipine is distributed into milk.¹

Plasma Protein Binding

Approximately 93%.¹

Elimination

Metabolism

Amlodipine is extensively (about 90%) metabolized to inactive metabolites in the liver.¹

Elimination Route

Amlodipine is excreted in urine as metabolites (60%) and unchanged drug (10%).¹

Half-life

Terminal elimination half-life of amlodipine is 30–50 hours.¹

Special Populations

In geriatric patients, amlodipine clearance decreased and AUC increased about 40–60%.¹

In pediatric patients 6–17 years of age, weight-adjusted clearance similar to values in adults.¹

In patients with hepatic impairment, amlodipine clearance decreased and AUC increased about 40–60%.¹

In patients with moderate to severe heart failure, amlodipine clearance decreased and AUC increased about 40–60%.¹

Stability

Storage

Oral

Tablets

Amlodipine: Tight, light-resistant containers at 15–30°C.¹

Amlodipine/perindopril, amlodipine/valsartan, and amlodipine/valsartan/hydrochlorothiazide fixed combinations: 25ºC (may be exposed to 15–30ºC); protect from moisture.¹¹³ ¹³⁰ ¹³³

Amlodipine/atorvastatin, amlodipine/olmesartan, and amlodipine/olmesartan/hydrochlorothiazide fixed combinations: 25°C (may be exposed to 15–30°C).¹⁰⁷ ¹³² ¹³⁴

Amlodipine/telmisartan fixed combination: Original blister packs at 25ºC (may be exposed to 15–30ºC); protect from light and moisture.¹²⁹ Do not remove from blister pack until immediately before administration.¹²⁹

Capsules

Amlodipine/benazepril fixed combination: Tight container at 25ºC (may be exposed to 15–30ºC).²¹

Actions

Amlodipine inhibits transmembrane influx of extracellular calcium ions across the membranes of myocardial cells and vascular smooth muscle cells, without changing serum calcium concentrations.¹
Amlodipine is a peripheral arterial vasodilator; acts directly on vascular smooth muscle causing reduction in peripheral vascular resistance and BP.¹
Amlodipine reduces total peripheral resistance (afterload) and rate pressure product and thus myocardial oxygen demand at any given level of exercise in patients with exertional angina.¹
Amlodipine blocks constriction and restores blood flow in coronary arteries in response to calcium, potassium, epinephrine, serotonin, and thromboxane A₂ analog in animal studies and human vessels in vitro.¹

Advice to Patients

When amlodipine is used in fixed combination with other drugs, importance of informing patients of important cautionary information about the concomitant agent(s).²¹ ¹⁰⁷ ¹¹³ ¹²⁹ ¹³⁰ ¹³² ¹³³ ¹³⁴
Importance of not removing amlodipine/telmisartan fixed-combination tablets from blister pack until immediately before administration.¹²⁹
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹
Importance of advising 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.

amLODIPine Besylate
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	2.5 mg (of amlodipine)*	Amlodipine Besylate Tablets
			Norvasc	Pfizer
		5 mg (of amlodipine)*	Amlodipine Besylate Tablets
			Norvasc	Pfizer
		10 mg (of amlodipine)*	Amlodipine Besylate Tablets
			Norvasc	Pfizer

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

amLODIPine Besylate Combinations
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	2.5 mg (of amlodipine) with Benazepril Hydrochloride 10 mg*	Amlodipine Besylate and Benazepril Hydrochloride Capsules
			Lotrel	Novartis
		5 mg (of amlodipine) with Benazepril Hydrochloride 10 mg*	Amlodipine Besylate and Benazepril Hydrochloride Capsules
			Lotrel	Novartis
		5 mg (of amlodipine) with Benazepril Hydrochloride 20 mg*	Amlodipine Besylate and Benazepril Hydrochloride Capsules
			Lotrel	Novartis
		5 mg (of amlodipine) with Benazepril Hydrochloride 40 mg*	Amlodipine Besylate and Benazepril Hydrochloride Capsules
			Lotrel	Novartis
		10 mg (of amlodipine) with Benazepril Hydrochloride 20 mg*	Amlodipine Besylate and Benazepril Hydrochloride Capsules
			Lotrel	Novartis
		10 mg (of amlodipine) with Benazepril Hydrochloride 40 mg*	Amlodipine Besylate and Benazepril Hydrochloride Capsules
			Lotrel	Novartis
	Tablets	2.5 mg (of amlodipine) with Perindopril Arginine 3.5 mg	Prestalia	Symplmed
		5 mg (of amlodipine) with Olmesartan Medoxomil 20 mg	Azor	Daiichi-Sankyo
		5 mg (of amlodipine) with Olmesartan Medoxomil 40 mg	Azor	Daiichi-Sankyo
		5 mg (of amlodipine) with Perindopril Arginine 7 mg	Prestalia	Symplmed
		10 mg (of amlodipine) with Olmesartan Medoxomil 20 mg	Azor	Daiichi-Sankyo
		10 mg (of amlodipine) with Olmesartan Medoxomil 40 mg	Azor	Daiichi-Sankyo
		10 mg (of amlodipine) with Perindopril Arginine 14 mg	Prestalia	Symplmed
	Tablets, film-coated	2.5 mg (of amlodipine) with Atorvastatin Calcium 10 mg (of atorvastatin)*	Amlodipine Besylate and Atorvastatin Calcium Tablets
			Caduet	Pfizer
		2.5 mg (of amlodipine) with Atorvastatin Calcium 20 mg (of atorvastatin)*	Amlodipine Besylate and Atorvastatin Calcium Tablets
			Caduet	Pfizer
		2.5 mg (of amlodipine) with Atorvastatin Calcium 40 mg (of atorvastatin)*	Amlodipine Besylate and Atorvastatin Calcium Tablets
			Caduet	Pfizer
		5 mg (of amlodipine) with Atorvastatin Calcium 10 mg (of atorvastatin)*	Amlodipine Besylate and Atorvastatin Calcium Tablets
			Caduet	Pfizer
		5 mg (of amlodipine) with Atorvastatin Calcium 20 mg (of atorvastatin)*	Amlodipine Besylate and Atorvastatin Calcium Tablets
			Caduet	Pfizer
		5 mg (of amlodipine) with Atorvastatin Calcium 40 mg (of atorvastatin)*	Amlodipine Besylate and Atorvastatin Calcium Tablets
			Caduet	Pfizer
		5 mg (of amlodipine) with Atorvastatin Calcium 80 mg (of atorvastatin)*	Amlodipine Besylate and Atorvastatin Calcium Tablets
			Caduet	Pfizer
		5 mg (of amlodipine) with Hydrochlorothiazide 12.5 mg and Olmesartan Medoxomil 20 mg	Tribenzor	Daiichi Sankyo
		5 mg (of amlodipine) with Hydrochlorothiazide 12.5 mg and Olmesartan Medoxomil 40 mg	Tribenzor	Daiichi Sankyo
		5 mg (of amlodipine) with Hydrochlorothiazide 12.5 mg and Valsartan 160 mg*	Amlodipine Besylate, Valsartan, and Hydrochlorothiazide Tablets
			Exforge HCT	Novartis
		5 mg (of amlodipine) with Hydrochlorothiazide 25 mg and Olmesartan Medoxomil 40 mg	Tribenzor	Daiichi Sankyo
		5 mg (of amlodipine) with Hydrochlorothiazide 25 mg and Valsartan 160 mg*	Amlodipine Besylate, Valsartan, and Hydrochlorothiazide Tablets
			Exforge HCT	Novartis
		5 mg (of amlodipine) with Valsartan 160 mg*	Amlodipine Besylate and Valsartan Tablets
			Exforge	Novartis
		5 mg (of amlodipine) with Valsartan 320 mg*	Amlodipine Besylate and Valsartan Tablets
			Exforge	Novartis
		10 mg (of amlodipine) with Atorvastatin Calcium 10 mg (of atorvastatin)*	Amlodipine Besylate and Atorvastatin Calcium Tablets
			Caduet	Pfizer
		10 mg (of amlodipine) with Atorvastatin Calcium 20 mg (of atorvastatin)*	Amlodipine Besylate and Atorvastatin Calcium Tablets
			Caduet	Pfizer
		10 mg (of amlodipine) with Atorvastatin Calcium 40 mg (of atorvastatin)*	Amlodipine Besylate and Atorvastatin Calcium Tablets
			Caduet	Pfizer
		10 mg (of amlodipine) with Atorvastatin Calcium 80 mg (of atorvastatin)*	Amlodipine Besylate and Atorvastatin Calcium Tablets
			Caduet	Pfizer
		10 mg (of amlodipine) with Hydrochlorothiazide 12.5 mg and Olmesartan Medoxomil 40 mg	Tribenzor	Daiichi Sankyo
		10 mg (of amlodipine) with Hydrochlorothiazide 12.5 mg and Valsartan 160 mg*	Amlodipine Besylate, Valsartan, and Hydrochlorothiazide Tablets
			Exforge HCT	Novartis
		10 mg (of amlodipine) with Hydrochlorothiazide 25 mg and Olmesartan Medoxomil 40 mg	Tribenzor	Daiichi Sankyo
		10 mg (of amlodipine) with Hydrochlorothiazide 25 mg and Valsartan 160 mg*	Amlodipine Besylate, Valsartan, and Hydrochlorothiazide Tablets
			Exforge HCT	Novartis
		10 mg (of amlodipine) with Hydrochlorothiazide 25 mg and Valsartan 320 mg*	Amlodipine Besylate, Valsartan, and Hydrochlorothiazide Tablets
			Exforge HCT	Novartis
		10 mg (of amlodipine) with Valsartan 160 mg*	Amlodipine Besylate and Valsartan Tablets
			Exforge	Novartis
		10 mg (of amlodipine) with Valsartan 320 mg*	Amlodipine Besylate and Valsartan Tablets
			Exforge	Novartis
	Tablets, multilayer	5 mg (of amlodipine) with Telmisartan 40 mg*	Telmisartan and Amlodipine Besylate Tablets
			Twynsta	Boehringer Ingelheim
		5 mg (of amlodipine) with Telmisartan 80 mg*	Telmisartan and Amlodipine Besylate Tablets
			Twynsta	Boehringer Ingelheim
		10 mg (of amlodipine) with Telmisartan 40 mg*	Telmisartan and Amlodipine Besylate Tablets
			Twynsta	Boehringer Ingelheim
		10 mg (of amlodipine) with Telmisartan 80 mg*	Telmisartan and Amlodipine Besylate Tablets
			Twynsta	Boehringer Ingelheim

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

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73. Brown MJ, Palmer CR, Castaigne A et al. Morbidity and mortality in patients randomized to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet. 2000; 356:366-72. http://www.ncbi.nlm.nih.gov/pubmed/10972368?dopt=AbstractPlus

74. Vincent J, Harris SI, Foulds G et al. Lack of effect on grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine. Br J Clin Pharmacol. 2000; 50:455-63. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2014412&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/11069440?dopt=AbstractPlus

75. Vincent J, Harris S, Foulds G et al. Amlodipine and grapefruit juice. Br J Clin Pharmacol. 2002; 53:406. Letter http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1874279&blobtype=pdf

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81. 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

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129. Boehringer Ingelhein Pharmaceuticals, Inc. Twynsta (telmisartan and amlodipine besylate) tablets prescribing information. Ridgefield, CT; 2014 Dec.

130. Symplmed, LLC. Prestalia (perindopril arginine and amlodipine besylate) tablets prescribing information. Cincinatti, OH; 2015 Jan.

132. Daiichi Sankyo, Inc. Tribenzor (olmesartan medoxomil, amlodipine, hydrochlorothiazide) tablets prescribing information. Parsippany, NJ; 2014 Sep.

133. Novartis Pharmaceuticals Corporation. Exforge HCT (amlodipine, valsartan, hydrochlorothiazide) tablets prescribing information. East Hanover, NJ; 2014 Sep.

134. Daiichi Sankyo, Inc. Azor (amlodipine and olmesartan medoxomil) tablets prescribing information. Parsippany, NJ; 2014 Sep.

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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

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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.

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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

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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.

538. Pickering TG, White WB, American Society of Hypertension Writing Group. When and how to use self (home) and ambulatory blood pressure monitoring. J Am Soc Hypertens. 2008 May-Jun; 2:119-24.

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

800. Yancy CW, Jessup M, Bozkurt B et al. 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2016; :.

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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

1205. Aronow WS, Frishman WH. Implications of the New National Guidelines for Hypertension. Cardiol Rev. 2018 Mar/Apr; 26:55-61. http://www.ncbi.nlm.nih.gov/pubmed/29419560?dopt=AbstractPlus

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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

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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

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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

b. AHFS drug information 2019. McEvoy GK, ed. Nifedipine. Bethesda, MD: American Society of Hospital Pharmacists; 2019:.

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