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AMLODIPINE BESYLATE- amlodipine besylate tablet RedPharm Drug, Inc.
amlodipine 10mg HIGHLIGHTS OF PRESCRIBING INFORMATION hese highlights do not include all the information needed to use AMLODIPINE BESYLATE TABLETS safely and effectively. See full prescribing information for AMLODIPINE BESYLATE TABLETS. AMLODIPINE BESYLATE TABLETS for oral administration Initial U.S. Approval: 1987 INDICATIONS AND USAGE Amlodipine besylate tablets is a calcium channel blocker and may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of:
- Hypertension (1.1) Amlodipine besylate tablets 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.
- Coronary Artery Disease (1.2) Chronic Stable Angina Vasospastic Angina (Prinzmetal’s or Variant Angina) Angiographically Documented Coronary Artery Disease in patients without heart failure or an ejection fraction < 40% DOSAGE AND ADMINISTRATION Adult recommended starting dose: 5 mg once daily with maximum dose 10 mg once daily. (2.1) Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg once daily. (2.1) Pediatric starting dose: 2.5 mg to 5 mg once daily. (2.2) Important Limitation: Doses in excess of 5 mg daily have not been studied in pediatric patients. (2.2) DOSAGE FORMS AND STRENGTHS Tablets: 2.5 mg, 5 mg, and 10 mg (3) CONTRAINDICATIONS Known sensitivity to amlodipine (4) WARNINGS AND PRECAUTIONS
- Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. However, acute hypotension is unlikely. (5.1)
- Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of Amlodipine besylate tablets,USP, particularly in patients with severe obstructive coronary artery disease. (5.2)
- Titrate slowly in patients with severe hepatic impairment. (5.3) ADVERSE REACTIONS Most common adverse reaction to amlodipine is edema which occurred in a dose related manner. Other adverse experiences not dose related but reported with an incidence
1.0% are fatigue, nausea, abdominal pain, and somnolence. (6) To report SUSPECTED ADVERSE REACTIONS,contact Ascend Laboratories, LLC at 1- 877-ASC-RX01 (877-272-7901)or FDA at 1-800-FDA-1088 or WWW.FDA.GOV/MEDWATCH DRUG INTERACTIONS Do not exceed doses greater than 20 mg daily of simvastatin. (7.2) USE IN SPECIFIC POPULATIONS Pregnancy: Use only if the potential benefit justifies the risk. (8.1) Nursing: Discontinue when administering amlodipine besylate. (8.3) Pediatric: Effect on patients less than 6 years old is not known. (8.4) Geriatric: Start dosing at the low end of the dose range. (8.5) See 17 for FDA-approved patient labeling. Revised: 11/ FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS & USAGE 1.1 Hypertension 1.2 Coronary Artery Disease (CAD) 2 DOSAGE & ADMINISTRATION 2.1 Adults 2.2 Children 3 DOSAGE FORMS & STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Hypotension 5.2 Increased Angina or Myocardial Infarction 5.3 Patients with Hepatic Failure 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience 6.2 Postmarketing Experience 7 DRUG INTERACTIONS 7.1 Impact of Other Drugs on Amlodipine 7.2 Impact of Amlodipine on Other Drugs 8 USE IN SPECIFIC POPULATIONS
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 may be used alone or in combination with other antihypertensive agents. 1.2 Coronary Artery Disease (CAD) Chronic Stable Angina Amlodipine besylate tablets is indicated for the symptomatic treatment of chronic stable angina. Amlodipine besylate tablets may be used alone or in combination with other antianginal agents. Vasospastic Angina (Prinzmetal’s or Variant Angina) Amlodipine besylate tablets is indicated for the treatment of confirmed or suspected vasospastic angina. Amlodipine besylate tablets 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 is indicated to reduce the risk of hospitalization for angina and to reduce the risk of a coronary revascularization procedure. 2 DOSAGE & ADMINISTRATION 2.1 Adults The usual initial antihypertensive oral dose of Amlodipine besylate tablets 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 tablets 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. Angina: 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. Coronary artery disease: 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 [see CLINICAL STUDIES (14.4)]. 2.2 Children The effective antihypertensive oral dose in pediatric patients ages 6 to 17 years is 2. 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)]. 3 DOSAGE FORMS & STRENGTHS Tablets: 2.5 mg white to off white, round,flat-faced, beveled edge tablets '211' debossed on one side and plain on theother side. Tablets: 5mg white to off white, round, flat-faced, beveled edge tablets '210' debossedon one side and plain on the other side. Tablets: 10 mg white to off white, round,flat-faced, beveled edge tablets '209' debossed on one side and plain on theother side. 4 CONTRAINDICATIONS Amlodipine besylate tablets are contraindicated in patients with known sensitivity to amlodipine. 5 WARNINGS AND PRECAUTIONS 5.1 Hypotension 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 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 to patients with severe hepatic impairment. 6 ADVERSE REACTIONS 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,USP has been evaluated for safety in more than 11, patients in U.S. and foreign clinical trials. In general, treatment with Amlodipine besylate tablets,USP was well-tolerated at doses up to 10 mg daily. Most adverse reactions reported during therapy with Amlodipine besylate tablets,USP were of mild or moderate
Nausea
Abdominal pain
Somnolence
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: Amlodipine Placebo Male=% (N=1218) Female=% (N=512) Male=% (N=914) Female=% (N=336) Edema
Flushing
Palpitations
Somnolence
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 besylate tablets,USP 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.
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. 8.3 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. 8.4 Pediatric Use Amlodipine besylate tablets (2.5 to 5 mg daily) is effective in lowering blood pressure in patients 6 to 17 years [see CLINICAL STUDIES (14.1)]. Effect of amlodipine on blood pressure in patients less than 6 years of age is not known. 8.5 Geriatric 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 to 60%, and a lower initial dose may be required [see DOSAGE AND ADMINISTRATION (2.1)]. 10 OVERDOSAGE Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional overdosage of amlodipine is limited. 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. If massive overdose should occur, initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential. Should hypotension occur, provide cardiovascular support including elevation of the extremities and the judicious administration of fluids. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors (such as phenylephrine) with attention to circulating volume and urine output. As amlodipine is highly protein bound,
hemodialysis is not likely to be of benefit. 11 DESCRIPTION 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, monobenzenesulphonate. Its molecular formula is C20H25ClN2O5•C6H6O3S, and its structural formula is: [amlodipine-str-2] 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, USP are formulated as white tablets equivalent to 2.5, 5, and 10 mg of amlodipine for oral administration. In addition to the active ingredient, amlodipine besylate, each tablet contains the following inactive ingredients: microcrystalline cellulose, dibasic calcium phosphate anhydrous, sodium starch glycolate, colloidal silicon dioxide and magnesium stearate. 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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 smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. The precise mechanisms by which amlodipine relieves angina have not been fully delineated, but are thought to include the following: Exertional Angina: In patients with exertional angina, amlodipine reduces the total peripheral resistance (afterload) against which the heart works and reduces the rate pressure product, and thus myocardial oxygen demand, at any given level of exercise.
Drug interactions Sildenafil: When amlodipine and sildenafil were used in combination, each agent independently exerted its own blood pressure lowering effect [see DrugInteractions (7.1)]. 12.3 Pharmacokinetics After oral administration of therapeutic doses of amlodipine, absorption produces peak plasma concentrations between 6 and 12 hours. Absolute bioavailability has been estimated to be between 64 and 90%. The bioavailability of amlodipine is not altered by the presence of food. Amlodipine is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine. Ex vivo studies have shown that approximately 93% of the circulating drug is bound to plasma proteins in hypertensive patients. Elimination from the plasma is biphasic with a terminal elimination half-life of about 30 to 50 hours. Steady-state plasma levels of amlodipine are reached after 7 to 8 days of consecutive daily dosing. The pharmacokinetics of amlodipine are not significantly influenced by renal impairment. Patients with renal failure may therefore receive the usual initial dose. Elderly patients and patients with hepatic insufficiency have decreased clearance of amlodipine with a resulting increase in AUC of approximately 40 to 60%, and a lower initial dose may be required. A similar increase in AUC was observed in patients with moderate to severe heart failure. Drug interactions In vitro data indicate that amlodipine has no effect on the human plasma protein binding of digoxin, phenytoin, warfarin, and indomethacin. Impact of other drugs on amlodipine Co-administered cimetidine, magnesium-and aluminum hydroxide antacids, sildenafil, and grapefruit juice have no impact on the exposure to amlodipine. CYP3A 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 CYP3A (e.g., itraconazole, clarithromycin) may increase the plasma concentrations of amlodipine to a greater extent [see DRUG INTERACTIONS (7.1)]. Impact of amlodipine on other drugs Co-administered amlodipine does not affect the exposure to atorvastatin, digoxin, ethanol and the warfarin prothrombin response time. Simvastatin: Co-administration 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 [see DRUG INTERACTIONS (7.2)].
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 [see DRUG INTERACTIONS (7.2)]. Tacrolimus: A prospective study in healthy Chinese volunteers (N=9) with CYP3A expressers showed a 2.5-to 4-fold increase in tacrolimus exposure when concomitantly administered with amlodipine compared to tacrolimus alone. This finding was not observed in CYP3A5 non-expressers (N= 6). However, a 3-fold increase in plasma exposure to tacrolimus in a renal transplant patient (CYP3A5 non-expresser) upon initiation of amlodipine for the treatment of post-transplant hypertension resulting in reduction of tacrolimus dose has been reported. Irrespective of the CYP3A5 genotype status, the possibility of an interaction cannot be excluded with these drugs [see DRUG INTERACTIONS (7.2)]. 12.4 Pediatric Patients Sixty-two hypertensive patients aged 6 to 17 years received doses of amlodipine between 1.25 mg and 20 mg. Weight-adjusted clearance and volume of distribution were similar to values in adults. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Rats and mice treated with amlodipine maleate in the diet for up to two years, at concentrations calculated to provide daily dosage levels of 0.5, 1.25, and 2.5 amlodipine mg/kg/day, showed no evidence of a carcinogenic effect of the drug. For the mouse, the highest dose was, on a mg/m2 basis, similar to the maximum recommended human dose of 10 mg amlodipine/day.3 For the rat, the highest dose was, on a mg/m2 basis, about twice the maximum recommended human dose. Mutagenicity studies conducted with amlodipine maleate revealed no drug related effects at either the gene or chromosome level. There was no effect on the fertility of rats treated orally with amlodipine maleate (males for 64 days and females for 14 days prior to mating) at doses up to 10 mg amlodipine/kg/day (8 times the maximum recommended human dose3 of 10 mg/day on a mg/m2 basis). 3 Based on patient weight of 50 kg 14 CLINICAL STUDIES 14.1 Effects in Hypertension Adult Patients The antihypertensive efficacy of amlodipine has been demonstrated in a total of 15 double-blind, placebo-controlled, randomized studies involving 800 patients on amlodipine and 538 on placebo. Once daily administration produced statistically significant placebo-corrected reductions in supine and standing blood pressures at 24 hours postdose, averaging about 12/6 mmHg in the standing position and 13/7 mmHg in the supine position in patients with mild to moderate hypertension. Maintenance of the
without left main coronary disease and without heart failure or an ejection fraction <40%. Patients (76% males, 89% Caucasian, 93% enrolled at U.S. sites, 89% with a history of angina, 52% without PCI, 4% with PCI and no stent, and 44% with a stent) were randomized to double-blind treatment with either amlodipine besylate tablets (5 to 10 mg once daily) or placebo in addition to standard care that included aspirin (89%), statins (83%), beta-blockers (74%), nitroglycerin (50%), anti-coagulants (40%), and diuretics (32%), but excluded other calcium channel blockers. The mean duration of follow-up was 19 months. The primary endpoint was the time to first occurrence of one of the following events: hospitalization for angina pectoris, coronary revascularization, myocardial infarction, cardiovascular death, resuscitated cardiac arrest, hospitalization for heart failure, stroke/TIA, or peripheral vascular disease. A total of 110 (16.6%) and 151 (23.1%) first events occurred in the amlodipine besylate tablets and placebo groups, respectively, for a hazard ratio of 0.691 (95% CI: 0.540 to 0.884, p = 0.003). The primary endpoint is summarized in Figure 1 below. The outcome of this study was largely derived from the prevention of hospitalizations for angina and the prevention of revascularization procedures (see Table 1). Effects in various subgroups are shown in Figure 2. In an angiographic substudy (n=274) conducted within CAMELOT, there was no significant difference between amlodipine and placebo on the change of atheroma volume in the coronary artery as assessed by intravascular ultrasound. Figure 1 -Kaplan-Meier Analysis of Composite Clinical Outcomes for Amlodipine versus Placebo [Figure 1] Figure 2 – Effects on Primary Endpoint of Amlodipine versus Placebo across Sub-Groups [Figure 2] Table 1 below summarizes the significant composite endpoint and clinical outcomes from the composites of the primary endpoint. The other components of the primary endpoint including cardiovascular death, resuscitated cardiac arrest, myocardial infarction, hospitalization for heart failure, stroke/TIA, or peripheral vascular disease did not demonstrate a significant difference between amlodipine and placebo. Table 1. Incidence of Significant Clinical Outcomes for CAMELOT Clinical Outcomes N (%) Amlodipine (N=663) Placebo (N=655) Risk Reduction (p-value) Composite CV Endpoint 110 (16.6) 151 (23.1) 31% (0.003)
Hospitalization for Angina* 51 (7.7) 84 (12.8) 42% (0.002) Coronary Revascularization* 78 (11.8) 103 (15.7) 27% (0.033) *Total patients with these events 14.5 Studies in Patients with Heart Failure Amlodipine has been compared to placebo in four 8 to 12 week studies of patients with NYHA Class II/III heart failure, involving a total of 697 patients. In these studies, there was no evidence of worsened heart failure based on measures of exercise tolerance, NYHA classification, symptoms, or left ventricular ejection fraction. In a long-term (follow-up at least 6 months, mean 13.8 months) placebo-controlled mortality/morbidity study of amlodipine 5 to 10 mg in 1153 patients with NYHA Classes III (n=931) or IV (n=222) heart failure on stable doses of diuretics, digoxin, and ACE inhibitors, amlodipine had no effect on the primary endpoint of the study which was the combined endpoint of all-cause mortality and cardiac morbidity (as defined by life-threatening arrhythmia, acute myocardial infarction, or hospitalization for worsened heart failure), or on NYHA classification, or symptoms of heart failure. Total combined all-cause mortality and cardiac morbidity events were 222/571 (39%) for patients on amlodipine and 246/583 (42%) for patients on placebo; the cardiac morbid events represented about 25% of the endpoints in the study. Another study (PRAISE-2) randomized patients with NYHA Class III (80%) or IV (20%) heart failure without clinical symptoms or objective evidence of underlying ischemic disease, on stable doses of ACE inhibitors (99%), digitalis (99%), and diuretics (99%), to placebo (n=827) or amlodipine (n=827) and followed them for a mean of 33 months. There was no statistically significant difference between amlodipine and placebo in the primary endpoint of all-cause mortality (95% confidence limits from 8% reduction to 29% increase on amlodipine). With amlodipine there were more reports of pulmonary edema. 16 HOW SUPPLIED/STORAGE AND HANDLING 2.5 mg Tablets Amlodipine besylate tablets, USP 2.5 mg (amlodipine besylate equivalent to 2.5 mg of amlodipine per tablet) are supplied as white to off white, round, flat-faced, beveled edge tablets '211' debossed on one side and plain on the other side and supplied as follows: NDC 67877-197-90 Bottle of 90 NDC 67877-197-05 Bottle of 500
It can be used by itself or with other medicines to treat these conditions. High Blood Pressure (hypertension) High blood pressure comes from blood pushing too hard against your blood vessels. Amlodipine besylate relaxes your blood vessels, which lets your blood flow more easily and helps lower your blood pressure. Drugs that lower blood pressure lower your risk of having a stroke or heart attack. Angina Angina is a pain or discomfort that keeps coming back when part of your heart does not get enough blood. Angina feels like a pressing or squeezing pain, usually in your chest under the breastbone. Sometimes you can feel it in your shoulders, arms, neck, jaws, or back. Amlodipine besylate can relieve this pain. Who should not use amlodipine besylate? Do not use amlodipine besylate if you are allergic to amlodipine (the active ingredient in amlodipine besylate tablets), or to the inactive ingredients. Your doctor or pharmacist can give you a list of these ingredients. What should I tell my doctor before taking amlodipine besylate? Tell your doctor about any prescription and non-prescription medicines you are taking, including natural or herbal remedies. Tell your doctor if you: ever had heart disease ever had liver problems are pregnant, or plan to become pregnant. Your doctor will decide if amlodipine besylate is the best treatment for you. are breastfeeding. Do not breastfeed while taking amlodipine besylate. You can stop breastfeeding or take a different medicine. How should I take amlodipine besylate tablets, USP? Take amlodipine besylate tablets, USP once a day, with or without food. It may be easier to take your dose if you do it at the same time every day, such as with breakfast or dinner, or at bedtime. Do not take more than one dose of amlodipine besylate at a time. If you miss a dose, take it as soon as you remember. Do not take amlodipine besylate if it has been more than 12 hours since you missed your last dose. Wait and take the next dose at your regular time. Other medicines: You can use nitroglycerin and amlodipine besylate together. If you take nitroglycerin for angina, don't stop taking it while you are taking amlodipine besylate. While you are taking amlodipine besylate, do not stop taking your other prescription medicines, including any other blood pressure medicines, without talking to your doctor. If you took too much amlodipine besylate, call your doctor or Poison Control Center, or go to the nearest hospital emergency room right away. What should I avoid while taking amlodipine besylate? Do not breastfeed. It is not known if amlodipine besylate will pass through your milk. Do not start any new prescription or non-prescription medicines or supplements, unless you check with your doctor first.
What are the possible side effects of amlodipine besylate? Amlodipine besylate may cause the following side effects. Most side effects are mild or moderate: swelling of your legs or ankles tiredness, extreme sleepiness stomach pain, nausea dizziness flushing (hot or warm feeling in your face) arrhythmia (irregular heartbeat) heart palpitations (very fast heartbeat) muscle rigidity, tremor and/or abnormal muscle movement It is rare, but when you first start taking amlodipine besylate or increase your dose, you may have a heart attack or your angina may get worse. If that happens, call your doctor right away or go directly to a hospital emergency room. Tell your doctor if you are concerned about any side effects you experience. These are not all the possible side effects of amlodipine besylate. For a complete list, ask your doctor or pharmacist. How do I store amlodipine besylate tablets, USP? Keep amlodipine besylate tablets, USP away from children. Store amlodipine besylate tablets, USP at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F) (see USP Controlled Room Temperature). Keep amlodipine besylate tablets, USP out of the light. Do not store in the bathroom. Keep amlodipine besylate tablets, USP in a dry place. General advice about amlodipine besylate tablets, USP Sometimes, doctors will prescribe a medicine for a condition that is not written in the patient information leaflets. Only use amlodipine besylate tablets, USP the way your doctor told you to. Do not give amlodipine besylate tablets, USP to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or doctor for information about amlodipine besylate tablets, USP. Manufactured in India by: ALKEM LABORATORIES LTD. H.O.: ALKEM HOUSE, Senapati Bapat marg, Lower Parel, Mumbai - 400 013. Distributed by: Ascend Laboratories, LLC Parsippany, NJ 07054 Revised Date:November, PT1453-
