Details
| Stereochemistry | RACEMIC |
| Molecular Formula | C20H25ClN2O5.ClH |
| Molecular Weight | 445.337 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.CCOC(=O)C1=C(COCCN)NC(C)=C(C1C2=C(Cl)C=CC=C2)C(=O)OC
InChI
InChIKey=BSBOZVBRVBLCLO-UHFFFAOYSA-N
InChI=1S/C20H25ClN2O5.ClH/c1-4-28-20(25)18-15(11-27-10-9-22)23-12(2)16(19(24)26-3)17(18)13-7-5-6-8-14(13)21;/h5-8,17,23H,4,9-11,22H2,1-3H3;1H
| Molecular Formula | C20H25ClN2O5 |
| Molecular Weight | 408.876 |
| Charge | 0 |
| Count |
|
| Stereochemistry | RACEMIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Optical Activity | ( + / - ) |
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular mooth muscle cells than on cardiac muscle cells. Amlodipine is indicated for the treatment of hypertension and coronary artery disease.
Originator
Sources: http://www.drugfuture.com/chemdata/amlodipine.html | http://www.pfizer.com/about/history/all
Curator's Comment: # Pfizer
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 57.0 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | NORVASC Approved UseAmlodipine besylate tablets USP are calcium channel blocker and may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of: •Hypertension (1.1) о Amlodipine besylate tablets USP are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. •Coronary Artery Disease (1.2) о Chronic Stable Angina о Vasospastic Angina (Prinzmetal's or Variant Angina) о Angiographically Documented Coronary Artery Disease in patients without heart failure or an ejection fraction < 40% 1.1 Hypertension Amlodipine besylate tablets USP are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including amlodipine besylate. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Amlodipine besylate tablets USP may be used alone or in combination with other antihypertensive agents. 1.2 Coronary Artery Disease (CAD) Chronic Stable Angina Amlodipine besylate tablets USP are indicated for the symptomatic treatment of chronic stable angina. Amlodipine besylate tablets USP may be used alone or in combination with other antianginal agents. Vasospastic Angina (Prinzmetal's or Variant Angina) Amlodipine besylate tablets USP are indicated for the treatment of confirmed or suspected vasospastic angina. Amlodipine besylate tablets USP may be used as monotherapy or in combination with other antianginal agents. Angiographically Documented CAD In patients with recently documented CAD by angiography and without heart failure or an ejection fraction <40%, amlodipine besylate tablets USP are indicated to reduce the risk of hospitalization for angina and to reduce the risk of a coronary revascularization procedure. Launch Date1992 |
|||
| Primary | NORVASC Approved UseAmlodipine besylate tablets USP are calcium channel blocker and may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of: •Hypertension (1.1) о Amlodipine besylate tablets USP are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. •Coronary Artery Disease (1.2) о Chronic Stable Angina о Vasospastic Angina (Prinzmetal's or Variant Angina) о Angiographically Documented Coronary Artery Disease in patients without heart failure or an ejection fraction < 40% 1.1 Hypertension Amlodipine besylate tablets USP are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including amlodipine besylate. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Amlodipine besylate tablets USP may be used alone or in combination with other antihypertensive agents. 1.2 Coronary Artery Disease (CAD) Chronic Stable Angina Amlodipine besylate tablets USP are indicated for the symptomatic treatment of chronic stable angina. Amlodipine besylate tablets USP may be used alone or in combination with other antianginal agents. Vasospastic Angina (Prinzmetal's or Variant Angina) Amlodipine besylate tablets USP are indicated for the treatment of confirmed or suspected vasospastic angina. Amlodipine besylate tablets USP may be used as monotherapy or in combination with other antianginal agents. Angiographically Documented CAD In patients with recently documented CAD by angiography and without heart failure or an ejection fraction <40%, amlodipine besylate tablets USP are indicated to reduce the risk of hospitalization for angina and to reduce the risk of a coronary revascularization procedure. Launch Date1992 |
|||
| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7867683 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
3 μg/L |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
5.9 μg/L |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
10.4 μg/L |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
3.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8112371 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
10.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8112371 |
5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
114 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7867683 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
187 μg × h/L |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
238 μg × h/L |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
464 μg × h/L |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
169 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8112371 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
214 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8112371 |
5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
48 h |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
36 h |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
37 h |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
41 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8112371 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
47 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8112371 |
5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
AMLODIPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2% |
AMLODIPINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
75 mg single, oral (mean) Overdose |
unhealthy, 42 years n = 1 Health Status: unhealthy Condition: Hypertension Age Group: 42 years Sex: F Population Size: 1 Sources: |
Disc. AE: Sinus tachycardia, Metabolic acidosis... AEs leading to discontinuation/dose reduction: Sinus tachycardia (1 patient) Sources: Metabolic acidosis (1 patient) Hypocalcemia (1 patient) |
10 mg 1 times / day steady, oral (min) Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy, adult n = 1250 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 1250 Sources: |
Disc. AE: Headache... AEs leading to discontinuation/dose reduction: Headache (1.5%) Sources: |
10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy, adult n = 268 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 268 Sources: |
DLT: Edema, Dizziness... Dose limiting toxicities: Edema (10.8%) Sources: Dizziness (3.4%) Flushing (2.6%) Palpitation (4.5%) |
2.5 mg 1 times / day steady, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: steady Dose: 2.5 mg, 1 times / day Sources: |
unhealthy, adult n = 275 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 275 Sources: |
DLT: Edema, Dizziness... Dose limiting toxicities: Edema (1.8%) Sources: Dizziness (1.1%) Flushing (0.7%) Palpitation (0.7%) |
5 mg 1 times / day steady, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: |
unhealthy, adult n = 296 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 296 Sources: |
DLT: Edema, Dizziness... Dose limiting toxicities: Edema (3%) Sources: Dizziness (3.4%) Flushing (1.4%) Palpitation (1.4%) |
5.6 mg 1 times / day steady, oral (mean) Recommended Dose: 5.6 mg, 1 times / day Route: oral Route: steady Dose: 5.6 mg, 1 times / day Sources: |
unhealthy, adult n = 231 Health Status: unhealthy Condition: Hypertension, Pregnancy Age Group: adult Sex: F Population Size: 231 Sources: |
Other AEs: Neonatal disorder NOS... |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Hypocalcemia | 1 patient Disc. AE |
75 mg single, oral (mean) Overdose |
unhealthy, 42 years n = 1 Health Status: unhealthy Condition: Hypertension Age Group: 42 years Sex: F Population Size: 1 Sources: |
| Metabolic acidosis | 1 patient Disc. AE |
75 mg single, oral (mean) Overdose |
unhealthy, 42 years n = 1 Health Status: unhealthy Condition: Hypertension Age Group: 42 years Sex: F Population Size: 1 Sources: |
| Sinus tachycardia | 1 patient Disc. AE |
75 mg single, oral (mean) Overdose |
unhealthy, 42 years n = 1 Health Status: unhealthy Condition: Hypertension Age Group: 42 years Sex: F Population Size: 1 Sources: |
| Headache | 1.5% Disc. AE |
10 mg 1 times / day steady, oral (min) Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy, adult n = 1250 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 1250 Sources: |
| Edema | 10.8% DLT |
10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy, adult n = 268 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 268 Sources: |
| Flushing | 2.6% DLT |
10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy, adult n = 268 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 268 Sources: |
| Dizziness | 3.4% DLT |
10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy, adult n = 268 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 268 Sources: |
| Palpitation | 4.5% DLT |
10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy, adult n = 268 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 268 Sources: |
| Flushing | 0.7% DLT |
2.5 mg 1 times / day steady, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: steady Dose: 2.5 mg, 1 times / day Sources: |
unhealthy, adult n = 275 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 275 Sources: |
| Palpitation | 0.7% DLT |
2.5 mg 1 times / day steady, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: steady Dose: 2.5 mg, 1 times / day Sources: |
unhealthy, adult n = 275 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 275 Sources: |
| Dizziness | 1.1% DLT |
2.5 mg 1 times / day steady, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: steady Dose: 2.5 mg, 1 times / day Sources: |
unhealthy, adult n = 275 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 275 Sources: |
| Edema | 1.8% DLT |
2.5 mg 1 times / day steady, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: steady Dose: 2.5 mg, 1 times / day Sources: |
unhealthy, adult n = 275 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 275 Sources: |
| Flushing | 1.4% DLT |
5 mg 1 times / day steady, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: |
unhealthy, adult n = 296 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 296 Sources: |
| Palpitation | 1.4% DLT |
5 mg 1 times / day steady, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: |
unhealthy, adult n = 296 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 296 Sources: |
| Edema | 3% DLT |
5 mg 1 times / day steady, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: |
unhealthy, adult n = 296 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 296 Sources: |
| Dizziness | 3.4% DLT |
5 mg 1 times / day steady, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: |
unhealthy, adult n = 296 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 296 Sources: |
| Neonatal disorder NOS | 11 patient | 5.6 mg 1 times / day steady, oral (mean) Recommended Dose: 5.6 mg, 1 times / day Route: oral Route: steady Dose: 5.6 mg, 1 times / day Sources: |
unhealthy, adult n = 231 Health Status: unhealthy Condition: Hypertension, Pregnancy Age Group: adult Sex: F Population Size: 231 Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| moderate [IC50 11.3 uM] | ||||
| no [IC50 >133 uM] | ||||
| no [IC50 >133 uM] | ||||
| no [IC50 >133 uM] | ||||
| no [IC50 >133 uM] | ||||
| no | ||||
| strong [Ki 0.13 uM] | ||||
| strong [Ki 1.95 uM] | ||||
| strong | ||||
| weak [IC50 57 uM] | ||||
| weak | ||||
| weak | ||||
| weak | ||||
| weak | yes (co-administration study) Comment: A prospective study in renal transplant patients (N=11) showed on an average of 40% increase in trough cyclosporine levels when concomitantly treated with amlodipine. Page: (Label 2) 24 |
|||
| yes [IC50 22 uM] | ||||
| yes [Inhibition 2 uM] | ||||
| yes | ||||
| yes | ||||
Page: (Label 2) 24 |
yes | yes (co-administration study) Comment: A prospective study in healthy Chinese volunteers (N=9) with CYP3A5 expressers showed a 2.5-to 4-fold increase in tacrolimus exposure when concomitantly administered with amlodipine. Page: (Label 2) 24 |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| likely | ||||
| major | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205003Orig1s000ClinPharmR.pdf#page=26 Page: (ClinPharm) 21, 26, (Label 2) 23 |
major | yes (co-administration study) Comment: Co-administration of the moderate CYP3A inhibitor diltiazem increases the exposure to amlodipine 1.6-fold., Erythromycin co-administration in healthy volunteers did not significantly change amlodipine systemic exposure. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205003Orig1s000ClinPharmR.pdf#page=26 Page: (ClinPharm) 21, 26, (Label 2) 23 |
||
| yes | yes (pharmacogenomic study) Comment: Following administration of amlodipine, blood pressure in all patients decreased. The magnitude of the change in blood pressure varied among patients. Individuals with the CYP3A5*1/*3 polymorphism exhibited the highest change in blood pressure, followed by CYP3A5*4, CYP3A5*1/*1, and CYP3A5*6 |
|||
| yes | yes (pharmacogenomic study) Comment: Amlodipine pharmacokinetics was affected by the genetic polymorphisms of the ABCB1 gene in humans. |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| The unique binding properties of amlodipine: a long-acting calcium antagonist. | 1991 Aug |
|
| Amlodipine treatment of cocaine dependence. | 1999 Apr-Jun |
|
| Effects of amlodipine on nitric oxide synthase mRNA expression and coronary microcirculation in prolonged nitric oxide blockade-induced hypertensive rats. | 1999 Aug |
|
| Telangiectasia and gingival hyperplasia as side-effects of amlodipine (Norvasc) in a 3-year-old girl. | 1999 Jul |
|
| [Effects of benidipine hydrochloride (Coniel) on blood pressure, heart rate and plasma norepinephrine concentration in spontaneously hypertensive rats]. | 1999 May |
|
| Restenosis and clinical outcome in patients treated with amlodipine after angioplasty: results from the Coronary AngioPlasty Amlodipine REStenosis Study (CAPARES). | 2000 Mar 1 |
|
| Role of transforming growth factor-beta1 in the progression of chronic allograft nephropathy. | 2001 |
|
| Comparative effects of amlodipine and nifedipine GITS during treatment and after missing two doses. | 2001 Feb |
|
| Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators. | 2001 Jun |
|
| Syncope following oral chloroquine administration in a hypertensive patient controlled on amlodipine. | 2002 Apr |
|
| Double-blind, placebo-controlled crossover comparison of five classes of antihypertensive drugs. | 2002 Apr |
|
| [Toxic hepatitis caused by amlodipine]. | 2002 Feb |
|
| Combination therapy of amlodipine/benazepril versus monotherapy of amlodipine in a practice-based setting. | 2002 Jun |
|
| Is psychosis exacerbated by modafinil? | 2002 Mar |
|
| Reversible ageusia induced by losartan: a case report. | 2002 May |
|
| Severity of hypertension affects improved resistance artery endothelial function by angiotensin-converting enzyme inhibition. | 2002 May |
|
| Arterial hypertension with brachydactyly in a 15-year-old boy. | 2003 Aug |
|
| Effects of amlodipine on ischemia after percutaneous transluminal coronary angioplasty: secondary results of the Coronary Angioplasty Amlodipine Restenosis (CAPARES) Study. | 2003 Jun |
|
| Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. | 2003 May |
|
| Platelet morphology and plasma indices of platelet activation in essential hypertension: effects of amlodipine-based antihypertensive therapy. | 2004 |
|
| Irbesartan: a review of its use in hypertension and in the management of diabetic nephropathy. | 2004 |
|
| Acute renal failure and hepatotoxicity associated with roxithromycin. | 2004 Apr |
|
| Effect of slow-release indapamide and perindopril compared with amlodipine on 24-hour blood pressure and left ventricular mass in hypertensive patients of African ancestry. | 2004 May |
|
| Exercise-related syncope induced by vasodilator therapy in an elderly hypertensive patient. | 2005 Feb |
|
| Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
|
| Indapamide sustained release: a review of its use in the treatment of hypertension. | 2006 |
|
| Pharmacoeconomic consequences of amlodipine besylate therapy in patients undergoing PTCA. | 2006 Mar |
|
| A novel stealth liposomal topotecan with amlodipine: apoptotic effect is associated with deletion of intracellular Ca2+ by amlodipine thus leading to an enhanced antitumor activity in leukemia. | 2006 May 15 |
|
| Results of a comparative, phase III, 12-week, multicenter, prospective, randomized, double-blind assessment of the efficacy and tolerability of a fixed-dose combination of telmisartan and amlodipine versus amlodipine monotherapy in Indian adults with stage II hypertension. | 2007 Dec |
|
| Differential effects of dihydropyridine calcium antagonists on doxorubicin-induced nephrotoxicity in rats. | 2007 Feb 28 |
|
| Vildagliptin, a novel dipeptidyl peptidase IV inhibitor, has no pharmacokinetic interactions with the antihypertensive agents amlodipine, valsartan, and ramipril in healthy subjects. | 2008 Jan |
|
| Synergistic effect of amlodipine and atorvastatin on blood pressure, left ventricular remodeling, and C-reactive protein in hypertensive patients with primary hypercholesterolemia. | 2008 Mar |
|
| Amlodipine inhibits cell proliferation via PKD1-related pathway. | 2008 May 2 |
Sample Use Guides
Adult recommended starting dose: 5 mg once daily with maximum dose
10 mg once daily. Small, fragile, or elderly patients, or patients with hepatic
insufficiency may be started on 2.5 mg once daily.
Pediatric starting dose: 2.5 mg to 5 mg once daily. Important Limitation: Doses in excess of 5 mg daily have not been studied.
Route of Administration:
Oral
| Substance Class |
Chemical
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ENANTIOMER -> RACEMATE |
