Product Elements:
Nifedipine nifedipine nifedipine nifedipine lactose monohydrate cellulose, microcrystalline hypromellose, unspecified magnesium stearate polyvinyl alcohol, unspecified talc titanium dioxide polyethylene glycol 3350 lecithin, soybean ferric oxide yellow ferrosoferric oxide novast;33
Drug Interactions:
Drug interactions nifedipine is mainly eliminated by metabolism and is a substrate of cyp3a. inhibitors and inducers of cyp3a can impact the exposure to nifedipine and consequently its desirable and undesirable effects. in vitro and in vivo data indicate that nifedipine can inhibit the metabolism of drugs that are substrates of cyp3a, thereby increasing the exposure to other drugs. nifedipine is a vasodilator, and co-administration of other drugs affecting blood pressure may result in pharmacodynamic interactions.
Indications and Usage:
Indications and usage nifedipine extended-release tablets, usp are indicated for the treatment of hypertension. it may be used alone or in combination with other antihypertensive agents.
Warnings:
Warnings excessive hypotension although in most patients the hypotensive effect of nifedipine is modest and well tolerated, occasional patients have had excessive and poorly tolerated hypotension. these responses have usually occurred during initial titration or at the time of subsequent upward dosage adjustment, and may be more likely in patients using concomitant beta-blockers. severe hypotension and/or increased fluid volume requirements have been reported in patients who received immediate release capsules together with a beta-blocking agent and who underwent coronary artery bypass surgery using high dose fentanyl anesthesia. the interaction with high dose fentanyl appears to be due to the combination of nifedipine and a beta-blocker, but the possibility that it may occur with nifedipine alone, with low doses of fentanyl, in other surgical procedures, or with other narcotic analgesics cannot be ruled out. in nifedipine-treated patients where surgery using high dose fentanyl anesthe
Read more...sia is contemplated, the physician should be aware of these potential problems and, if the patient's condition permits, sufficient time (at least 36 hours) should be allowed for nifedipine to be washed out of the body prior to surgery. increased angina and/or myocardial infarction rarely, patients, particularly those who have severe obstructive coronary artery disease, have developed well-documented increased frequency, duration and/or severity of angina or acute myocardial infarction upon starting nifedipine or at the time of dosage increase. the mechanism of this effect is not established. beta-blocker withdrawal when discontinuing a beta-blocker it is important to taper its dose, if possible, rather than stopping abruptly before beginning nifedipine. patients recently withdrawn from beta blockers may develop a withdrawal syndrome with increased angina, probably related to increased sensitivity to catecholamines. initiation of nifedipine treatment will not prevent this occurrence and on occasion has been reported to increase it. congestive heart failure rarely, patients (usually while receiving a beta-blocker) have developed heart failure after beginning nifedipine. patients with tight aortic stenosis may be at greater risk for such an event, as the unloading effect of nifedipine would be expected to be of less benefit to these patients, owing to their fixed impedance to flow across the aortic valve.
Dosage and Administration:
Dosage and administration dosage should be adjusted according to each patient's needs. it is recommended that nifedipine extended-release tablets, usp be administered orally once daily on an empty stomach. the nifedipine extended-release tablet, usp is an extended release dosage form and tablets should be swallowed whole, not bitten or divided. in general, titration should proceed over a 7-14 day period starting with 30 mg once daily. upward titration should be based on therapeutic efficacy and safety. the usual maintenance dose is 30 mg to 60 mg once daily. titration to doses above 90 mg daily is not recommended. if discontinuation of the nifedipine extended-release tablet is necessary, sound clinical practice suggests that the dosage should be decreased gradually with close physician supervision. co-administration of nifedipine with grapefruit juice is to be avoided (see clinical pharmacology and precautions ). care should be taken when dispensing nifedipine extended-release tablets
Read more...to assure that the extended release dosage form has been prescribed.
Contraindications:
Contraindications concomitant administration with strong p450 inducers, such as rifampin, are contraindicated since the efficacy of nifedipine tablets could be significantly reduced. (see precautions , drug interactions. ) nifedipine must not be used in cases of cardiogenic shock. nifedipine extended-release tablets are contraindicated in patients with a known hypersensitivity to any component of the tablet.
Adverse Reactions:
Adverse reactions the incidence of adverse events during treatment with nifedipine extendedrelease tablets in doses up to 90 mg daily were derived from multi-center placebo-controlled clinical trials in 370 hypertensive patients. atenolol 50 mg once daily was used concomitantly in 187 of the 370 patients on nifedipine extendedrelease tablets and in 64 of the 126 patients on placebo. all adverse events reported during nifedipine extendedrelease tablets therapy were tabulated independently of their causal relationship to medication. the most common adverse event reported with nifedipine extendedrelease tablets was peripheral edema. this was dose related and the frequency was 18% on nifedipine extendedrelease tablets 30 mg daily, 22% on nifedipine extendedrelease tablets 60 mg daily and 29% on nifedipine extendedrelease tablets 90 mg daily versus 10% on placebo. other common adverse events reported in the above placebo-controlled trials include: where the frequency of adverse events with
Read more...nifedipine extended-release tablets and placebo is similar, causal relationship cannot be established. the following adverse events were reported with an incidence of 3% or less in daily doses up to 90 mg: body as a whole/systemic: chest pain, leg pain central nervous system: paresthesia, vertigo dermatologic: rash gastrointestinal: constipation musculoskeletal: leg cramps respiratory: epistaxis, rhinitis urogenital: impotence, urinary frequency other adverse events reported with an incidence of less than 1.0% were: body as a whole/systemic: allergic reaction, asthenia, cellulitis, substernal chest pain, chills, facial edema, lab test abnormal, malaise, neck pain, pelvic pain, pain, photosensitivity reaction cardiovascular: atrial fibrillation, bradycardia, cardiac arrest, extrasystole, hypotension, migraine, palpitations, phlebitis, postural hypotension, tachycardia, cutaneous angiectases central nervous system: anxiety, confusion, decreased libido, depression, hypertonia, hypesthesia, insomnia, somnolence dermatologic: angioedema, petechial rash, pruritus, sweating gastrointestinal: abdominal pain, diarrhea, dry mouth, dysphagia, dyspepsia, eructation, esophagitis, flatulence, gastrointestinal disorder, gastrointestinal hemorrhage, ggt increased, gum disorder, gum hemorrhage, vomiting hematologic: eosinophilia, lymphadenopathy metabolic: gout, weight loss musculoskeletal: arthralgia, arthritis, joint disorder, myalgia, myasthenia respiratory: dyspnea, increased cough, rales, pharyngitis, stridor special senses: abnormal vision, amblyopia, conjunctivitis, diplopia, eye disorder, eye hemorrhage, tinnitus urogenital/reproductive: dysuria, kidney calculus, nocturia, breast engorgement, polyuria, urogenital disorder, erectile dysfunction (ed) the following adverse events have been reported rarely in patients given nifedipine in coat core or other formulations: allergenic hepatitis, alopecia, anaphylactic reaction, anemia, arthritis with ana (+), depression, erythromelalgia, exfoliative dermatitis, fever, gingival hyperplasia, gynecomastia, hyperglycemia, jaundice, leukopenia, mood changes, muscle cramps, nervousness, paranoid syndrome, purpura, shakiness, sleep disturbances, stevens-johnson syndrome, syncope, taste perversion, thrombocytopenia, toxic epidermal necrolysis, transient blindness at the peak of plasma level, tremor and urticaria. to report suspected adverse reactions, please call ingenus pharmaceuticals, llc toll-free at 1-877-748-1970 or fda at 1-800-fda-1088 or www.fda.gov/medwatch. image3
Drug Interactions:
Drug interactions nifedipine is mainly eliminated by metabolism and is a substrate of cyp3a. inhibitors and inducers of cyp3a can impact the exposure to nifedipine and consequently its desirable and undesirable effects. in vitro and in vivo data indicate that nifedipine can inhibit the metabolism of drugs that are substrates of cyp3a, thereby increasing the exposure to other drugs. nifedipine is a vasodilator, and co-administration of other drugs affecting blood pressure may result in pharmacodynamic interactions.
Use in Pregnancy:
Pregnancy
Pediatric Use:
Pediatric use the safety and effectiveness of nifedipine extended-release tablets in pediatric patients have not been established.
Geriatric Use:
Geriatric use although small pharmacokinetic studies have identified an increased half-life and increased c max and auc (see clinical pharmacology : pharmacokinetics and metabolism ), clinical studies of nifedipine 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.
Overdosage:
Overdosage experience with nifedipine overdosage is limited. symptoms associated with severe nifedipine overdosage include loss of consciousness, drop in blood pressure, heart rhythm disturbances, metabolic acidosis, hypoxia, cardiogenic shock with pulmonary edema. generally, overdosage with nifedipine leading to pronounced hypotension calls for active cardiovascular support including monitoring of cardiovascular and respiratory function, elevation of extremities, judicious use of calcium infusion, pressor agents and fluids. after oral ingestion, thorough gastric lavage is indicated, if necessary in combination with irrigation of the small intestine. in cases involving overdosage of a slow-release product like nifedipine, elimination must be as complete as possible, including from the small intestine, to prevent the subsequent absorption of the active substance. additional liquid or volume must be administered with caution because of the risk of fluid overload. clearance of nifedipine would be expected to be prolonged in patients with impaired liver function. since nifedipine is highly protein bound, dialysis is not likely to be of any benefit; however, plasmapheresis may be beneficial. there has been one reported case of massive overdosage with tablets of another extended release formulation of nifedipine. the main effects of ingestion of approximately 4800 mg of nifedipine in a young man attempting suicide as a result of cocaine-induced depression was initial dizziness, palpitations, flushing, and nervousness. within several hours of ingestion, nausea, vomiting, and generalized edema developed. no significant hypotension was apparent at presentation, 18 hours post ingestion. blood chemistry abnormalities consisted of a mild, transient elevation of serum creatinine, and modest elevations of ldh and cpk, but normal sgot. vital signs remained stable, no electrocardiographic abnormalities were noted and renal function returned to normal within 24 to 48 hours with routine supportive measures alone. no prolonged sequelae were observed. the effect of a single 900 mg ingestion of nifedipine capsules in a depressed anginal patient on tricyclic antidepressants was loss of consciousness within 30 minutes of ingestion, and profound hypotension, which responded to calcium infusion, pressor agents, and fluid replacement. a variety of ecg abnormalities were seen in this patient with a history of bundle branch block, including sinus bradycardia and varying degrees of av block. these dictated the prophylactic placement of a temporary ventricular pacemaker, but otherwise resolved spontaneously. significant hyperglycemia was seen initially in this patient, but plasma glucose levels rapidly normalized without further treatment. a young hypertensive patient with advanced renal failure ingested 280 mg of nifedipine capsules at one time, with resulting marked hypotension responding to calcium infusion and fluids. no av conduction abnormalities, arrhythmias, or pronounced changes in heart rate were noted, nor was there any further deterioration in renal function. bradycardiac heart rhythm disturbances may be treated symptomatically with Ã-sympathomimetics, and in life-threatening bradycardiac disturbances of heart rhythm temporary pacemaker therapy can be advisable.
Description:
Description nifedipine extended-release tablets, usp are an extended release tablet dosage form of the calcium channel blocker nifedipine. nifedipine is 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-dimethyl ester, c 17 h 18 n 2 o 6 , and has the structural formula: product meets usp dissolution test 10. nifedipine is a yellow crystalline substance, practically insoluble in water but soluble in ethanol. it has a molecular weight of 346.3. nifedipine extended release tablets contain either: 30, 60, or 90 mg of nifedipine for once-a-day oral administration. inert ingredients in the 30mg nifedipine extended-release tablet formulation are lactose monohydrate, microcrystalline cellulose, hypromellose, magnesium stearate, polyvinyl alcohol, talc, titanium dioxide, macrogol/polyethylene glycol 3350, lecithin (soy), iron oxide yellow and iron oxide black. inert ingredients in the 60mg nifedipine extended-release tablet formulation are lactose monohydrate, microcrystalline cellulose, hypromellose, magnesium stearate, polyvinyl alcohol, titanium dioxide, talc, macrogol/polyethylene glycol 3350, lecithin (soy), iron oxide red, iron oxide black and iron oxide yellow. inert ingredients in the 90mg nifedipine extended-release tablet formulation are: lactose monohydrate, microcrystalline cellulose, hypromellose, magnesium stearate, polyvinyl alcohol, iron oxide red, talc, macrogol/polyethylene glycol 3350, iron oxide yellow, titanium dioxide, lecithin (soy) and iron oxide black. image1
Clinical Pharmacology:
Clinical pharmacology nifedipine is a calcium ion influx inhibitor (slow-channel blocker or calcium ion antagonist) which inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. the contractile processes of vascular smooth muscle and cardiac muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. nifedipine selectively inhibits calcium ion influx across the cell membrane of vascular smooth muscle and cardiac muscle without altering serum calcium concentrations. mechanism of action the mechanism by which nifedipine reduces arterial blood pressure involves peripheral arterial vasodilatation and, consequently, a reduction in peripheral vascular resistance. the increased peripheral vascular resistance, an underlying cause of hypertension, results from an increase in active tension in the vascular smooth muscle. studies have demonstrated that the increase in active tension reflects an incr
Read more...ease in cytosolic free calcium. nifedipine is a peripheral arterial vasodilator which acts directly on vascular smooth muscle. the binding of nifedipine to voltage-dependent and possibly receptor-operated channels in vascular smooth muscle results in an inhibition of calcium influx through these channels. stores of intracellular calcium in vascular smooth muscle are limited and thus dependent upon the influx of extracellular calcium for contraction to occur. the reduction in calcium influx by nifedipine causes arterial vasodilation and decreased peripheral vascular resistance which results in reduced arterial blood pressure. pharmacokinetics and metabolism nifedipine is completely absorbed after oral administration. the bioavailability of nifedipine from nifedipine extended-release tablets relative to immediate release tablets is in the range of 84%-89%. after ingestion of nifedipine extended-release tablets under fasting conditions, plasma concentrations peak at about 2.5-5 hours with a second small peak or shoulder evident at approximately 6-12 hours post dose. the elimination half-life of nifedipine administered as nifedipine extended-release tablets is approximately 7 hours in contrast to the known 2 hour elimination half-life of nifedipine administered as an immediate release capsule. when nifedipine extended-release tablets are administered as multiples of 30 mg tablets over a dose range of 30 mg to 90 mg, the area under the curve (auc) is dose proportional; however, the peak plasma concentration for the 90 mg dose given as 3 x 30 mg is 29% greater than predicted from the 30 mg and 60 mg doses. two 30 mg nifedipine extended-release tablets may be interchanged with a 60 mg nifedipine extended-release tablet. three 30 mg nifedipine extended-release tablets, however, result in substantially higher cmax values than those after a single 90 mg nifedipine extended-release tablet. three 30 mg tablets should, therefore, not be considered interchangeable with a 90 mg tablet. once daily dosing of nifedipine extended-release tablets under fasting conditions results in decreased fluctuations in the plasma concentration of nifedipine when compared to t.i.d. dosing with immediate release nifedipine capsules. the mean peak plasma concentration of nifedipine following a 90 mg nifedipine extended-release tablet, administered under fasting conditions, is approximately 115 ng/ml. when nifedipine extended-release tablets are given immediately after a high fat meal in healthy volunteers, there is an average increase of 60% in the peak plasma nifedipine concentration, a prolongation in the time to peak concentration, but no significant change in the auc. plasma concentrations of nifedipine when nifedipine extended-release tablets are taken after a fatty meal result in slightly lower peaks compared to the same daily dose of the immediate release formulation administered in three divided doses. this may be, in part, because nifedipine extended-release tablets are less bioavailable than the immediate release formulation. nifedipine is extensively metabolized to highly water soluble, inactive metabolites accounting for 60% to 80% of the dose excreted in the urine. only traces (less than 0.1% of the dose) of the unchanged form can be detected in the urine. the remainder is excreted in the feces in metabolized form, most likely as a result of biliary excretion. nifedipine is metabolized via the cytochrome p450 3a4 system. drugs that are known to either inhibit or induce this enzyme system may alter the first pass or clearance of nifedipine. no studies have been performed with nifedipine extended-release tablets in patients with renal failure; however, significant alterations in the pharmacokinetics of nifedipine immediate release capsules have not been reported in patients undergoing hemodialysis or chronic ambulatory peritoneal dialysis. since the absorption of nifedipine from nifedipine extended-release tablets could be modified by renal disease, caution should be exercised in treating such patients. because nifedipine is metabolized via the cytochrome p450 3a4 system, its pharmacokinetics may be altered in patients with chronic liver disease. nifedipine extended-release tablets have not been studied in patients with hepatic disease; however, in patients with hepatic impairment (liver cirrhosis) nifedipine has a longer elimination half-life and higher bioavailability than in healthy volunteers. the degree of protein binding of nifedipine is high (92%-98%). protein binding may be greatly reduced in patients with renal or hepatic impairment. after administration of nifedipine extended-release tablets to healthy elderly men and women (age > 60 years), the mean c max is 36% higher and the average plasma concentration is 70% greater than in younger patients. in healthy subjects, the elimination half-life of a different sustained release nifedipine formulation was longer in elderly subjects (6.7 h) compared to young subjects (3.8 h) following oral administration. a decreased clearance was also observed in the elderly (348 ml/min) compared to young subjects (519 ml/min) following intravenous administration. co-administration of nifedipine with grapefruit juice results in up to a 2-fold increase in auc and c max, due to inhibition of cyp3a related first-pass metabolism. ingestion of grapefruit and grapefruit juice should be avoided while taking nifedipine. clinical studies nifedipine extended-release tablets produced dose-related decreases in systolic and diastolic blood pressure as demonstrated in two double-blind, randomized, placebo-controlled trials in which over 350 patients were treated with nifedipine extended-release tablets 30, 60 or 90 mg once daily for 6 weeks. in the first study, nifedipine extended-release tablets were given as monotherapy and in the second study, nifedipine extended-release tablets were added to a beta-blocker in patients not controlled on a beta-blocker alone. the mean trough (24 hours post-dose) blood pressure results from these studies are shown below: the trough/peak ratios estimated from 24 hour blood pressure monitoring ranged from 41%-78% for diastolic and 46%-91% for systolic blood pressure. hemodynamics like other slow-channel blockers, nifedipine exerts a negative inotropic effect on isolated myocardial tissue. this is rarely, if ever, seen in intact animals or man, probably because of reflex responses to its vasodilating effects. in man, nifedipine decreases peripheral vascular resistance which leads to a fall in systolic and diastolic pressures, usually minimal in normotensive volunteers (less than 5-10 mm hg systolic), but sometimes larger. with nifedipine extended-release tablets, these decreases in blood pressure are not accompanied by any significant change in heart rate. hemodynamic studies of the immediate release nifedipine formulation in patients with normal ventricular function have generally found a small increase in cardiac index without major effects on ejection fraction, left ventricular end-diastolic pressure (lvedp) or volume (lvedv). in patients with impaired ventricular function, most acute studies have shown some increase in ejection fraction and reduction in left ventricular filling pressure. electrophysiologic effects although, like other members of its class, nifedipine causes a slight depression of sinoatrial node function and atrioventricular conduction in isolated myocardial preparations, such effects have not been seen in studies in intact animals or in man. in formal electrophysiologic studies, predominantly in patients with normal conduction systems, nifedipine administered as the immediate release capsule has had no tendency to prolong atrioventricular conduction or sinus node recovery time, or to slow sinus rate. image2
Mechanism of Action:
Mechanism of action the mechanism by which nifedipine reduces arterial blood pressure involves peripheral arterial vasodilatation and, consequently, a reduction in peripheral vascular resistance. the increased peripheral vascular resistance, an underlying cause of hypertension, results from an increase in active tension in the vascular smooth muscle. studies have demonstrated that the increase in active tension reflects an increase in cytosolic free calcium. nifedipine is a peripheral arterial vasodilator which acts directly on vascular smooth muscle. the binding of nifedipine to voltage-dependent and possibly receptor-operated channels in vascular smooth muscle results in an inhibition of calcium influx through these channels. stores of intracellular calcium in vascular smooth muscle are limited and thus dependent upon the influx of extracellular calcium for contraction to occur. the reduction in calcium influx by nifedipine causes arterial vasodilation and decreased peripheral vascular resistance which results in reduced arterial blood pressure.
Clinical Studies:
Clinical studies nifedipine extended-release tablets produced dose-related decreases in systolic and diastolic blood pressure as demonstrated in two double-blind, randomized, placebo-controlled trials in which over 350 patients were treated with nifedipine extended-release tablets 30, 60 or 90 mg once daily for 6 weeks. in the first study, nifedipine extended-release tablets were given as monotherapy and in the second study, nifedipine extended-release tablets were added to a beta-blocker in patients not controlled on a beta-blocker alone. the mean trough (24 hours post-dose) blood pressure results from these studies are shown below: the trough/peak ratios estimated from 24 hour blood pressure monitoring ranged from 41%-78% for diastolic and 46%-91% for systolic blood pressure.
How Supplied:
How supplied nifedipine extended-release tablets, usp are supplied as 30 mg, 60 mg, and 90 mg round film coated tablets. the different strengths can be identified as follows: they are supplied by doh central pharmacy as follows: ndc strength quantity/form color source prod. code 53808-1118-1 30 mg 30 tablets in a blister pack yellow 50742-620 the tablets should be protected from light and moisture and stored at 20°-25°c (68°-77°f); [see usp controlled room temperature]. dispense in tight, light-resistant containers. image4 image6
Information for Patients:
Information for patients nifedipine extended-release tablets are an extended release tablet and should be swallowed whole and taken on an empty stomach. it should not be administered with food. do not chew, divide or crush tablets.
Package Label Principal Display Panel:
Package label label image for 53808-1118 30mg label image for 30mg