Amlodipine Besylate
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Deepika Beereddy, MBBS [2]
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Overview
Amlodipine Besylate is an antihypertensive agent that is FDA approved for the treatment of hypertension, coronary artery disease. Common adverse reactions include edema, fatigue, nausea, abdominal pain, and somnolence.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Hypertension
- Amlodipine besylate tablet, USP is 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 tablet, USP.
- 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.
- 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 tablet, USP may be used alone or in combination with other antihypertensive agents.
- Dosing information
- The usual initial antihypertensive oral dose of Amlodipine besylate tablet, USP is 5 mg once daily, and the maximum dose is 10 mg once daily.
- Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg once daily and this dose may be used when adding Amlodipine besylate tablet, USP to other antihypertensive therapy.
- Adjust dosage according to blood pressure goals. In general, wait 7 to 14 days between titration steps. Titrate more rapidly, however, if clinically warranted, provided the patient is assessed frequently.
Coronary Artery Disease (CAD)
Chronic Stable Angina
- Amlodipine besylate tablet, USP is indicated for the symptomatic treatment of chronic stable angina. Amlodipine besylate tablet, USP may be used alone or in combination with other antianginal agents.
- Dosing information:
- The recommended dose range for patients with coronary artery disease is 5 to 10 mg once daily. In clinical studies, the majority of patients required 10 mg
Vasospastic Angina (Prinzmetal's or Variant Angina)
- Amlodipine besylate tablet, USP is indicated for the treatment of confirmed or suspected vasospastic angina. Amlodipine besylate tablet, USP may be used as monotherapy or in combination with other antianginal agents.
- Dosing information:
- The recommended dose for chronic stable or vasospastic angina is 5 to 10 mg, with the lower dose suggested in the elderly and in patients with hepatic insufficiency. Most patients will require 10 mg for adequate effect.
Angiographically Documented CAD
- In patients with recently documented CAD by angiography and without heart failure or an ejection fraction <40%, Amlodipine besylate tablet, USP is indicated to reduce the risk of hospitalization for angina and to reduce the risk of a coronary revascularization procedure.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Amlodipine Besylate in adult patients.
Non–Guideline-Supported Use
- Congestive heart failure
- Diabetic nephropathy
- Disorder related to transplantation
- Kidney disease, Nondiabetic
- Left ventricular hypertrophy
- Raynaud's phenomenon
- Silent myocardial ischemia
- Systolic hypertension
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Hypertension
- Dosing information:
- 6 to 17 years of age: 2.5-5 mg ORALLY once daily
Safety and efficacy not established in pediatric patients younger than 6 years of age [3]
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Amlodipine Besylate in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Amlodipine Besylate in pediatric patients.
Contraindications
Amlodipine besylate tablet, USP is contraindicated in patients with known sensitivity to amlodipine.
Warnings
Hypotension
- Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. Because of the gradual onset of action, acute hypotension is unlikely.
Increased Angina or Myocardial Infarction
- Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease.
Patients with Hepatic Failure
- Because amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t1/2) is 56 hours in patients with impaired hepatic function, titrate slowly when administering amlodipine to patients with severe hepatic impairment.
Adverse Reactions
Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- Amlodipine has been evaluated for safety in more than 11,000 patients in U.S. and foreign clinical trials. In general, treatment with amlodipine was well-tolerated at doses up to 10 mg daily. Most adverse reactions reported during therapy with amlodipine were of mild or moderate severity. In controlled clinical trials directly comparing amlodipine (N=1730) at doses up to 10 mg to placebo (N=1250), discontinuation of amlodipine because of adverse reactions was required in only about 1.5% of patients and was not significantly different from placebo (about 1%). The most commonly reported side effects more frequent than placebo are reflected in the table below. The incidence (%) of side effects that occurred in a dose related manner are as follows:
- The following events occurred in <1% but >0.1% of patients in controlled clinical trials or under conditions of open trials or marketing experience where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship:
- Cardiovascular: arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, peripheral ischemia, syncope, tachycardia, vasculitis.
- Central and Peripheral Nervous System: hypoesthesia, neuropathy peripheral, paresthesia, tremor, vertigo.
- Gastrointestinal: anorexia, constipation, dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia.
- General: allergic reaction, asthenia,1 back pain, hot flushes, malaise, pain, rigors, weight gain, weight decrease.
- Musculoskeletal System: arthralgia, arthrosis, muscle cramps,1 myalgia.
- Psychiatric: sexual dysfunction (male1 and female), insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalization.
- Respiratory System: dyspnea,1 epistaxis.
- Skin and Appendages: angioedema, erythema multiforme, pruritus, 1 rash, 1 rash erythematous, rash maculopapular.
- Special Senses: abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus.
- Urinary System: micturition frequency, micturition disorder, nocturia.
- Autonomic Nervous System: dry mouth, sweating increased.
- Metabolic and Nutritional: hyperglycemia, thirst.
- Hemopoietic: leukopenia, purpura, thrombocytopenia.
1 These events occurred in less than 1% in placebo-controlled trials, but the incidence of these side effects was between 1% and 2% in all multiple dose studies.
- Amlodipine therapy has not been associated with clinically significant changes in routine laboratory tests. No clinically relevant changes were noted in serum potassium, serum glucose, total triglycerides, total cholesterol, HDL cholesterol, uric acid, blood urea nitrogen, or creatinine.
- In the CAMELOT and PREVENT studies, the adverse event profile was similar to that reported previously (see above), with the most common adverse event being peripheral edema.
Postmarketing Experience
- Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- The following postmarketing event has been reported infrequently where a causal relationship is uncertain: gynecomastia. In postmarketing experience, jaundice and hepatic enzyme elevations (mostly consistent with cholestasis or hepatitis), in some cases severe enough to require hospitalization, have been reported in association with use of amlodipine.
- Amlodipine has been used safely in patients with chronic obstructive pulmonary disease, well-compensated congestive heart failure, coronary artery disease, peripheral vascular disease, diabetes mellitus, and abnormal lipid profiles.
Drug Interactions
In Vitro Data
- In vitro data indicate that amlodipine has no effect on the human plasma protein binding of digoxin, phenytoin, warfarin, and indomethacin.
Cimetidine
- Coadministration of amlodipine with cimetidine did not alter the pharmacokinetics of amlodipine.
Grapefruit Juice
- Coadministration of 240 mL of grapefruit juice with a single oral dose of amlodipine 10 mg in 20 healthy volunteers had no significant effect on the pharmacokinetics of amlodipine.
Magnesium and Aluminum Hydroxide Antacid
- Coadministration of a magnesium and aluminum hydroxide antacid with a single dose of amlodipine had no significant effect on the pharmacokinetics of amlodipine.
Sildenafil
- A single 100 mg dose of sildenafil in subjects with essential hypertension had no effect on the pharmacokinetic parameters of amlodipine. When amlodipine and sildenafil were used in combination, each agent independently exerted its own blood pressure lowering effect.
Atorvastatin
- Coadministration of multiple 10 mg doses of amlodipine with 80 mg of atorvastatin resulted in no significant change in the steady-state pharmacokinetic parameters of atorvastatin.
Simvastatin
- Coadministration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.
Digoxin
- Coadministration of amlodipine with digoxin did not change serum digoxin levels or digoxin renal clearance in normal volunteers.
Ethanol (Alcohol)
- Single and multiple 10 mg doses of amlodipine had no significant effect on the pharmacokinetics of ethanol.
Warfarin
- Coadministration of amlodipine with warfarin did not change the warfarin prothrombin response time.
CYP3A4 Inhibitors
- Coadministration of a 180 mg daily dose of diltiazem with 5 mg amlodipine in elderly hypertensive patients resulted in a 60% increase in amlodipine systemic exposure. Erythromycin coadministration in healthy volunteers did not significantly change amlodipine systemic exposure. However, strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, ritonavir) may increase the plasma concentrations of amlodipine to a greater extent. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A4 inhibitors.
CYP3A4 Inducers
- No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Blood pressure should be closely monitored when amlodipine is coadministered with CYP3A4 inducers.
Cyclosporine
- 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.
Drug/Laboratory Test Interactions
- None known.
Use in Specific Populations
Pregnancy
- There are no adequate and well-controlled studies in pregnant women. Amlodipine should be used during pregnancy only if the potential benefit justifies the risk to the fetus.
- No evidence of teratogenicity or other embryo/fetal toxicity was found when pregnant rats and rabbits were treated orally with amlodipine maleate at doses up to 10 mg amlodipine/kg/day (respectively, 8 times2 and 23 times2 the maximum recommended human dose of 10 mg on a mg/m2 basis) during their respective periods of major organogenesis. However, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold) in rats receiving amlodipine maleate at a dose equivalent to 10 mg amlodipine/kg/day for 14 days before mating and throughout mating and gestation. Amlodipine maleate has been shown to prolong both the gestation period and the duration of labor in rats at this dose.
2 Based on patient weight of 50 kg.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Amlodipine Besylate in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Amlodipine Besylate during labor and delivery.
Nursing Mothers
- It is not known whether amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing be discontinued while Amlodipine is administered.
Pediatric Use
- Amlodipine (2.5 to 5 mg daily) is effective in lowering blood pressure in patients 6 to 17 years.
Effect of amlodipine on blood pressure in patients less than 6 years of age is not known.
Geriatic Use
Clinical studies of amlodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients have decreased clearance of amlodipine with a resulting increase of AUC of approximately 40–60%, and a lower initial dose may be required.
Gender
There is no FDA guidance on the use of Amlodipine Besylate with respect to specific gender populations.
Race
There is no FDA guidance on the use of Amlodipine Besylate with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Amlodipine Besylate in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Amlodipine Besylate in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Amlodipine Besylate in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Amlodipine Besylate in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Amlodipine Besylate Administration in the drug label.
Monitoring
There is limited information regarding Amlodipine Besylate Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Amlodipine Besylate and IV administrations.
Overdosage
There is limited information regarding Amlodipine Besylate overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Amlodipine Besylate Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Amlodipine Besylate Mechanism of Action in the drug label.
Structure
There is limited information regarding Amlodipine Besylate Structure in the drug label.
Pharmacodynamics
There is limited information regarding Amlodipine Besylate Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Amlodipine Besylate Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Amlodipine Besylate Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Amlodipine Besylate Clinical Studies in the drug label.
How Supplied
There is limited information regarding Amlodipine Besylate How Supplied in the drug label.
Storage
There is limited information regarding Amlodipine Besylate Storage in the drug label.
Images
Drug Images
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Patient Counseling Information
There is limited information regarding Amlodipine Besylate Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Amlodipine Besylate interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Amlodipine Besylate Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Amlodipine Besylate Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.