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Amlodipine Besylate

Class: Dihydropyridines
- Calcium-Channel Blocking Agents, Dihydropyridine
- Dihydropyridine Calcium-Channel Blocking Agents
- Calcium Antagonists
VA Class: CV200
CAS Number: 111470-99-6
Brands: Norvasc

Medically reviewed on Nov 5, 2018

Introduction

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

Uses for Amlodipine Besylate

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents);1 2 3 4 5 6 21 113 128 129 130 131 132 133 134 1200 may be used in fixed combination with aliskiren, aliskiren and hydrochlorothiazide, benazepril, olmesartan, olmesartan and hydrochlorothiazide, perindopril, telmisartan, valsartan, or valsartan and hydrochlorothiazide when such combined therapy is indicated.21 113 128 129 130 131 132 133 134

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 Besylate 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

Administer amlodipine in fixed combination with aliskiren (with or without hydrochlorothiazide) in a consistent manner relative to meals; administration with a high-fat meal decreases aliskiren absorption.128 131

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: 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/Aliskiren Fixed-combination
Oral

Fixed-combination amlodipine/aliskiren tablets may be used for initial treatment of hypertension in patients likely to require combination therapy with multiple antihypertensive agents to control BP.128

If the patient’s baseline BP is 157/100 mm Hg, the estimated probability of achieving SBP control (SBP <140 mm Hg) is 49, 62, or 74% and of achieving DBP control (DBP <90 mm Hg) is 50, 69, or 83% with aliskiren (300 mg daily) alone, amlodipine (10 mg daily) alone, or amlodipine combined with aliskiren (same dosages), respectively.128

Can use the fixed combination as a substitute for the individually administered drugs.128 Can switch to the fixed-combination preparation containing the corresponding individual doses of amlodipine and aliskiren; alternatively, can increase the dosage of one or both components for additional antihypertensive effects.128

If BP is not adequately controlled by monotherapy with amlodipine (or another dihydropyridine-derivative calcium-channel blocker) or aliskiren, can switch to amlodipine/aliskiren fixed combination.128

If dose-limiting adverse effects have developed during monotherapy with aliskiren or amlodipine, can switch to an amlodipine/aliskiren fixed-combination preparation containing a lower dose of that drug to achieve similar BP control.128

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 aliskiren 150 mg once daily.128

May adjust dosage after 2–4 weeks at current dosage, up to maximum of 10 mg of amlodipine and 300 mg of aliskiren once daily; most of the antihypertensive effect of a given dosage is achieved within 1–2 weeks after a change in dosage.128

Amlodipine/Aliskiren/Hydrochlorothiazide Fixed-combination
Oral

Manufacturer states that amlodipine/aliskiren/hydrochlorothiazide fixed-combination preparation should not be used for initial treatment of hypertension.131

Can switch to amlodipine/aliskiren/hydrochlorothiazide fixed-combination tablets if BP is not adequately controlled by combined therapy with any 2 of the following: dihydropyridine-derivative calcium-channel blockers, aliskiren, or thiazide diuretics.131

In patients who experience dose-limiting adverse effects of amlodipine, aliskiren, 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.131

Can use the fixed combination as a substitute for the individually titrated drugs.131

May increase dosage of the fixed combination after 2 weeks if additional BP control is needed (up to maximum of amlodipine 10 mg, aliskiren 300 mg, and hydrochlorothiazide 25 mg once daily).131

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

When used for initial therapy of hypertension in patients likely to require combination therapy with multiple antihypertensive agents, recommended initial dosage is amlodipine 2.5 mg and perindopril arginine 3.5 mg once daily.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

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 valsartan 160 mg once daily in those who are not volume depleted.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 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 antianginal 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 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: 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 aliskiren (with or without hydrochlorothiazide), 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.113 128 129 131 132 133 134

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 Clcr ≤30 mL/minute.21

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

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

Safety and efficacy of preparations containing amlodipine in fixed combination with aliskiren (with or without hydrochlorothiazide) or in fixed combination with valsartan (with or without hydrochlorothiazide) in patients with Clcr <30 mL/minute not established.113 128 131 133

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 21 107 113 128 129 131 132 133 134 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 aliskiren (with or without hydrochlorothiazide), 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.113 128 129 131 132 133 134

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 Besylate

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).21 107 113 128 129 130 131 132 133 134 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.21 107 113 128 129 130 131 132 133 134

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 aliskiren (with or without hydrochlorothiazide), atorvastatin, benazepril, olmesartan (with or without hydrochlorothiazide), perindopril, telmisartan, or valsartan (with or without hydrochlorothiazide) not established in children.21 107 113 128 129 130 131 132 133 134

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 aliskiren (with or without hydrochlorothiazide), 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.21 113 128 129 131 132 133 134

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 21 107 113 128 129 131 132 133 134 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

Interactions for Amlodipine Besylate

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).21 107 113 128 129 130 131 132 133 134

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 Besylate 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.1 107 113 128 129 130 132 133 134

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/aliskiren and amlodipine/aliskiren/hydrochlorothiazide fixed combinations: Original container at 25ºC (may be exposed to 15–30ºC); protect from heat and moisture.128 131

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).21 107 113 128 129 130 131 132 133 134

  • Importance of taking amlodipine/aliskiren or amlodipine/aliskiren/hydrochlorothiazide fixed-combination tablets in a consistent manner relative to meals.128 131

  • Importance of storing amlodipine/aliskiren or amlodipine/aliskiren/hydrochlorothiazide fixed-combination tablets in original container.128 131

  • 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 Aliskiren Hemifumarate 150 mg (of aliskiren)

Tekamlo

Novartis

5 mg (of amlodipine) with Aliskiren Hemifumarate 150 mg (of aliskiren) and Hydrochlorothiazide 12.5 mg

Amturnide

Novartis

5 mg (of amlodipine) with Aliskiren Hemifumarate 300 mg (of aliskiren)

Tekamlo

Novartis

5 mg (of amlodipine) with Aliskiren Hemifumarate 300 mg (of aliskiren) and Hydrochlorothiazide 12.5 mg

Amturnide

Novartis

5 mg (of amlodipine) with Aliskiren Hemifumarate 300 mg (of aliskiren) and Hydrochlorothiazide 25 mg

Amturnide

Novartis

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 Aliskiren Hemifumarate 150 mg (of aliskiren)

Tekamlo

Novartis

10 mg (of amlodipine) with Aliskiren Hemifumarate 300 mg (of aliskiren)

Tekamlo

Novartis

10 mg (of amlodipine) with Aliskiren Hemifumarate 300 mg (of aliskiren) and Hydrochlorothiazide 12.5 mg

Amturnide

Novartis

10 mg (of amlodipine) with Aliskiren Hemifumarate 300 mg (of aliskiren) and Hydrochlorothiazide 25 mg

Amturnide

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

AHFS DI Essentials™. © Copyright 2019, Selected Revisions November 5, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

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