DESCRIPTION
id: 12299C43-6A73-3B8A-5855-CDDDC77F0F6F
displayName: Description section
FDA Article Code: 34089-3
Amlodipine besylate is the besylate salt of amlodipine, a long-acting calcium channel blocker.Amlodipine besylate is chemically described as 3-Ethyl-5-methyl (±)-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate, monobenzene-sulphonate. Its molecular formula is C20H25CIN2O5•C6H6O3S, and its structural formula is:Amlodipine besylate is a white crystalline powder with a molecular weight of 567.1. It is slightly soluble in water and sparingly soluble in ethanol. Amlodipine besylate tablets are formulated as white tablets equivalent to 2.5 mg, 5 mg or 10 mg of amlodipine for oral administration. In addition to the active ingredient, amlodipine besylate, each tablet contains the following Inactive Ingredients: dibasic calcium phosphate (anhydrous), butylated hydroxytoluene, microcrystalline cellulose, sodium starch glycolate, magnesium stearate.
CONTRAINDICATIONS
id: 2E46D7A2-7E27-7A8B-64C9-D711B0646D3A
displayName: Contraindications section
FDA Article Code: 34070-3
Amlodipine is contraindicated in patients with known sensitivity to amlodipine.
ADVERSE REACTIONS
id: 168D57A5-72D7-DA9A-B493-E3239F5F0641
displayName: Adverse Reactions section
FDA Article Code: 34084-4
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) in doses up to 10 mg to placebo (N=1250), discontinuation of amlodipine due to adverse reactions was required in only about 1.5% of patients and was not significantly different from placebo (about 1%). The most common side effects are headache and edema. The incidence (%) of side effects which occurred in a dose related manner are as follows:
| Adverse Event |
2.5 mg
N=275 |
5 mg
N=296 |
10 mg
N=268 |
Placebo
N=520 |
| Edema |
1.8 |
3.0 |
10.8 |
0.6 |
| Dizziness |
1.1 |
3.4 |
3.4 |
1.5 |
| Flushing |
0.7 |
1.4 |
2.6 |
0.0 |
| Palpitation |
0.7 |
1.4 |
4.5 |
0.6 |
Other adverse experiences which were not clearly dose related but which were reported with an incidence greater than 1% in placebo-controlled clinical trials include the following:
Placebo-Controlled Studies
| |
Amlodipine (%)
(N=1730) |
PLACEBO (%)
(N=1250) |
| Headache |
7.3 |
7.8 |
| Fatigue |
4.5 |
2.8 |
| Nausea |
2.9 |
1.9 |
| Abdominal Pain |
1.6 |
0.3 |
| Somnolence |
1.4 |
0.6 |
For several adverse experiences that appear to be drug and dose related, there was a greater incidence in women than men associated with amlodipine treatment as shown in the following table:
| Adverse Event |
Amlodipine |
Placebo |
Male=%
(N=1218) |
Female=%
(N=512) |
Male=%
(N=914) |
Female=%
(N=336) |
| Edema |
5.6 |
14.6 |
1.4 |
5.1 |
| Flushing |
1.5 |
4.5 |
0.3 |
0.9 |
| Palpitations |
1.4 |
3.3 |
0.9 |
0.9 |
| Somnolence |
1.3 |
1.6 |
0.8 |
0.3 |
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, hypotension, peripheral ischemia, syncope, tachycardia, postural dizziness, postural hypotension, vasculitis.Central and Peripheral Nervous System: hypoesthesia, neuropathy peripheral, paresthesia, tremor, vertigo.Gastrointestinal: anorexia, constipation, dyspepsia,** dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia.General: allergic reaction, asthenia,** back pain, hot flushes, malaise, pain, rigors, weight gain, weight decrease.Musculoskeletal System: arthralgia, arthrosis, muscle cramps,** myalgia.Psychiatric: sexual dysfunction (male** and female), insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalization.Respiratory System: dyspnea,** epistaxis.Skin and Appendages: angioedema, erythema multiforme, pruritus,** rash,** rash erythematous, rash maculopapular.**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.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.The following events occurred in <0.1% of patients: cardiac failure, pulse irregularity, extrasystoles, skin discoloration, urticaria, skin dryness, alopecia, dermatitis, muscle weakness, twitching, ataxia, hypertonia, migraine, cold and clammy skin, apathy, agitation, amnesia, gastritis, increased appetite, loose stools, coughing, rhinitis, dysuria, polyuria, parosmia, taste perversion, abnormal visual accommodation, and xerophthalmia.Other reactions occurred sporadically and cannot be distinguished from medications or concurrent disease states such as myocardial infarction and angina.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 (see CLINICAL PHARMACOLOGY Clinical Studies Studies in Patients with Coronary Artery Disease) the adverse event profile was similar to that
reported previously (see above), with the most common adverse event being peripheral edema.
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.
OVERDOSAGE
id: 8DD7D55C-715E-84A4-06AD-F920D8E4EAC2
displayName: Overdosage section
FDA Article Code: 34088-5
Single oral doses of amlodipine maleate equivalent to 40 mg amlodipine/kg and 100 mg amlodipine/kg in mice and rats, respectively, caused deaths. Single oral amlodipine maleate doses equivalent to 4 or more mg amlodipine/kg or higher in dogs (11 or more times the maximum recommended human dose on a mg/m2 basis) caused a marked peripheral vasodilation and hypotension.Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional over-dosage of amlodipine is limited. Reports of intentional overdosage include a patient who ingested 250 mg and was asymptomatic and was not hospitalized; another (120 mg) was hospitalized, underwent gastric lavage and remained normotensive; the third (105 mg) was hospitalized and had hypotension (90/50 mmHg) which normalized following plasma expansion. A case of accidental drug overdose has been documented in a 19-month-old male who ingested 30 mg amlodipine (about 2 mg/kg). During the emergency room presentation, vital signs were stable with no evidence of hypotension, but a heart rate of 180 bpm. Ipecac was administered 3.5 hours after ingestion and on subsequent observation (overnight) no sequelae were noted. If massive overdose should occur, active cardiac and respiratory monitoring should be instituted. Frequent blood pressure measurements are essential. Should hypotension occur, cardiovascular support including elevation of the extremities and the judicious administration of fluids should be initiated. If hypotension remains unresponsive to these conservative measures, administration of vasopressors (such as phenylephrine) should be considered with attention to circulating volume and urine output. Intravenous calcium gluconate may help to reverse the effects of calcium entry blockade. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.
HOW SUPPLIED
id: A0557A28-1753-E506-6D28-469FAAB0AC37
displayName: How Supplied section
FDA Article Code: 34069-5
Amlodipine besylate tablets, 2.5 mg are white to off-white colored, diamond-shaped, flat-faced, beveled-edge tablets, debossed with 568 on one side and plain on the other side available as follows:Bottles of 90 NDC 57664-568-99
Bottles of 100 NDC 57664-568-88
Bottles of 500 NDC 57664-568-13
Bottles of 1000 NDC 57664-568-18Amlodipine besylate tablets, 5 mg are white to off-white colored, octagonal, flat-faced, beveled-edge tablets, debossed with 569 on one side and plain on the other side available as follows:Bottles of 90 NDC 57664-569-99
Bottles of 100 NDC 57664-569-88
Bottles of 500 NDC 57664-569-13
Bottles of 1000 NDC 57664-569-18Amlodipine besylate tablets, 10 mg are white to off-white colored, circular, flat-faced, beveled-edge tablets, debossed with 570 on one side and plain on the other side available as follows:Bottles of 90 NDC 57664-570-99
Bottles of 100 NDC 57664-570-88
Bottles of 500 NDC 57664-570-13
Bottles of 1000 NDC 57664-570-18Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) [See USP Controlled Room Temperature].Protect from light and moisture
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Manufactured by:
Caraco Pharmaceutical Laboratories, Ltd.
1150 Elijah McCoy Drive
Detroit, MI 48202C.S.No.: 5598T03
