AMLODIPINE BESYLATE- amlodipine besylate tablet
Northwind Pharmaceuticals, LLC
Amlodipine besylate tablets, USP are indicated for the treatment of hypertension. It 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 due to angina and to reduce the risk of a coronary revascularization procedure.
The usual initial antihypertensive oral dose of amlodipine besylate tablets is 5 mg once daily with a maximum dose of 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 tablets to other antihypertensive therapy.
Adjust dosage according to each patient’s need. In general, titration should proceed over 7 to 14 days so that the physician can fully assess the patient’s response to each dose level. Titration may proceed more rapidly, however, if clinically warranted, provided the patient is assessed frequently.
The recommended dose for chronic stable or vasospastic angina is 5 to10 mg, with the lower dose suggested in the elderly and in patients with hepatic insufficiency. Most patients will require 10 mg for adequate effect [see Adverse Reactions (6)].
The recommended dose range for patients with coronary artery disease is 5 to10 mg once daily. In clinical studies, the majority of patients required 10 mg [see Clinical Studies (14.4)].
The effective antihypertensive oral dose in pediatric patients ages 6 to 17 years is 2.5 mg to 5 mg once daily. Doses in excess of 5 mg daily have not been studied in pediatric patients [see Clinical Pharmacology (12.4), Clinical Studies (14.1)].
Amlodipine besylate tablets are contraindicated in patients with known sensitivity to amlodipine.
Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. Because of the gradual onset of action, acute hypotension is unlikely.
5.2. Increased Angina or Myocardial Infarction
Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine besylate tablets, particularly in patients with severe obstructive coronary artery disease.
5.3. Beta-Blocker Withdrawal
Amlodipine is not a beta-blocker and therefore gives no protection against the dangers of abrupt beta-blocker withdrawal; any such withdrawal should be by gradual reduction of the dose of beta-blocker.
5.4. Patients with Hepatic Failure
Because amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t 1/2) is 56 hours in patients with impaired hepatic function, titrate slowly when administering amlodipine besylate to patients with severe hepatic impairment.
6.1. 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 besylate tablets have been evaluated for safety in more than 11,000 patients in U.S. and foreign clinical trials. In general, treatment with amlodipine besylate tablets were well-tolerated at doses up to 10 mg daily. Most adverse reactions reported during therapy with amlodipine besylate tablets were of mild or moderate severity. In controlled clinical trials directly comparing amlodipine besylate tablets (N= 1730) at doses up to
10 mg to placebo (N= 1250), discontinuation of amlodipine besylate tablets 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 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, 1 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, 1rash, 1rash 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.
1These 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.
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 Studies (14.4)], the adverse event profile was similar to that reported previously (see above), with the most common adverse event being peripheral edema.
6.2. 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 besylate tablets have 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.
PLEASE VISIT THE FDA SITE TO VIEW THE MANUFACTURER’S COMPLETE DRUG INFORMATION INCLUDING CLINICAL TRIAL INFORMATION:
7.1. In Vitro Data
In vitro data indicate that amlodipine has no effect on the human plasma protein binding of digoxin, phenytoin, warfarin, and indomethacin.
Co-administration of amlodipine with cimetidine did not alter the pharmacokinetics of amlodipine.
7.3. Grapefruit Juice
Co-administration 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.
7.4. Magnesium and Aluminum Hydroxide Antacid
Co-administration of a magnesium and aluminum hydroxide antacid with a single dose of amlodipine besylate tablets had no significant effect on the pharmacokinetics of amlodipine.
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.
Co-administration 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.
Co-administration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in 77 % increase in exposure to simvastatin compared to simvastatin alone. Limit the dose of simvastatin in patient on amlodipine to 20 mg daily
Co-administration of amlodipine with digoxin did not change serum digoxin levels or digoxin renal clearance in normal volunteers.
7.9. Ethanol (Alcohol)
Single and multiple 10 mg doses of amlodipine had no significant effect on the pharmacokinetics of ethanol.
Co-administration of amlodipine with warfarin did not change the warfarin prothrombin response time.
7.11. CYP3A4 Inhibitors
Co-administration 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 co-administration 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 co-administered with CYP3A4 inhibitors.
7.12. CYP3A4 Inducers
No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A4 inducers.
7.13. Drug/Laboratory Test Interactions
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