Procardia (nifedipine)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Nifedipine is a 1,4-dihydropyridine-derivative calcium-channel blocking agent.
Nifedipine is a 1,4-dihydropyridine-derivative calcium-channel blocking agent that is structurally related to amlodipine and isradipine. The principal physiologic action of nifedipine is to inhibit the transmembrane influx of extracellular calcium ions across the membranes of myocardial cells and vascular smooth muscle cells, without changing serum calcium concentrations. Nifedipine is a peripheral arterial vasodilator; the drug acts directly on vascular smooth muscle causing a reduction in peripheral vascular resistance and blood pressure.
In patients with Prinzmetal variant angina (vasospastic angina), inhibition of spontaneous and ergonovine-induced coronary artery spasm by nifedipine results in increased myocardial oxygen delivery. Nifedipine regularly reduces arterial pressure at rest and at a given level of exercise by dilating peripheral arterioles and reducing the total peripheral resistance (afterload) and thus myocardial oxygen demand. In contrast to verapamil and diltiazem, nifedipine has little or no effect on sinoatrial (SA) and atrioventricular (AV) nodal conduction at therapeutic doses.
Nifedipine is available in various dosage forms, as capsules or two different extended-release tablet formulations (gastrointestinal therapeutic system (GITS) or coat-core (CC)). Nifedipine is rapidly and fully absorbed from the GI tract following oral administration of the drug as conventional capsules. Peak serum concentrations usually are reached within 30 minutes after oral administration as capsules.
Food appears to decrease the rate but not the extent of absorption of nifedipine as conventional capsules. The manufacturer states that relative oral bioavailability differs little if conventional nifedipine capsules are swallowed intact, bitten and swallowed, or bitten and held sublingually. However, some data indicate that the rate and extent of absorption of nifedipine following sublingual administration may be decreased substantially.
The oral bioavailability of nifedipine may be increased up to twofold in patients with liver cirrhosis.
The commercially available extended-release tablets of nifedipine (Procardia XL(R)) contain the drug in an oral osmotic delivery system formulation (elementary osmotic pump, gastrointestinal therapeutic system (GITS)). The osmotic delivery system consists of an osmotically active core (comprised of a layer containing the drug and a layer containing osmotically active but pharmacologically inert components) that is surrounded by a semipermeable membrane with a laser-drilled delivery orifice and is designed to deliver the drug at an approximately constant rate over a 24-hour period (approximately zero-order delivery). When exposed to water in the GI tract, water is drawn osmotically into the core at a controlled rate that is determined by the permeability of the outer membrane and the osmotic pressure of the core formulation; as water enters the formulation, a resulting suspension of the drug is pushed out the delivery orifice of the membrane into the GI tract.
Delivery of nifedipine from the formulation depends on the existence of an osmotic gradient between the fluid in the GI tract and the osmotically active core of the tablet, with drug delivery remaining approximately constant as long as the gradient is maintained and then declining to zero as the concentration inside the tablet falls below saturation. The rate of nifedipine delivery in the GI tract is independent of pH and GI motility. The inert tablet ingredients remain intact and are eliminated in feces.
Following oral administration of a single dose of the drug as extended-release GITS tablets, plasma nifedipine concentrations increase gradually, reaching a peak at approximately 6 hours, and bioavailability is approximately 65% of that achieved with the same doses administered orally as conventional capsules. Following multiple doses, oral bioavailability from the extended-release tablets increases to approximately 86% of that achieved with the same doses administered as conventional capsules. Steady state usually is achieved during the second day of therapy with a given dose as GITS extended-release tablets.
Administration of nifedipine extended-release GITS tablets (Procardia XL(R)) with food can increase the early rate of GI absorption but reportedly does not affect overall bioavailability. Substantial reductions in GI retention time for prolonged periods (e.g., in patients with short-bowel syndrome) can result in decreased absorption of nifedipine from extended-release tablets. Because orally administered nifedipine undergoes extensive metabolism on first pass through the liver, bioavailability of the drug from extended-release tablets is increased substantially in patients with liver cirrhosis and may be particularly increased in those with portacaval shunts.
Another commercially available nifedipine extended-release tablet preparation is composed of a slow-release outer coat and an immediate-release core; this preparation is also known as coat-core (CC). The bioavailability of nifedipine CC extended-release tablets relative to conventional nifedipine capsules is about 84-89%. Following oral administration of CC tablets in fasting individuals, peak plasma concentrations occur within 2.5-5 hours, with a small second peak (or ''shoulder'') occurring within 6-12 hours.
Following oral administration of CC extended-release nifedipine 30-mg tablets over a dosage range of 30-90 mg, the area under the plasma-concentration time curve (AUC) was proportional to the dose administered; however, peak plasma concentrations of the 90-mg dose (three 30-mg tablets) were 29% greater than that predicted from the 30- and 60-mg doses. The manufacturer of CC extended-release nifedipine states that two 30-mg CC extended-release tablets may be interchanged with one 60-mg CC extended-release tablet; however, three 30-mg CC extended-release tablets should not be considered interchangeable with one 90-mg CC extended-release tablet. Once-daily dosing of CC extended-release tablets, under fasting conditions, resulted in less fluctuation in plasma nifedipine concentrations when compared with 3-times-daily dosing with conventional nifedipine capsules.
Administration of CC extended-release tablets immediately after a high-fat meal increases peak plasma nifedipine concentrations by 60% and delays the time to peak plasma concentrations; however, no substantial changes in AUC occur. Peak plasma concentrations of nifedipine following administration of CC extended-release tablets after a high-fat meal are slightly lower than those achieved after administration of the same daily dosage given in 3 divided doses as conventional capsules; this difference may be attributed to the lower bioavailability of CC extended-release tablets compared with that of the capsules.
Binding of nifedipine to plasma proteins is concentration dependent and ranges from 92-98%. Protein binding may be reduced in patients with renal or hepatic (e.g., liver cirrhosis) impairment. In patients with normal renal and hepatic function, the plasma half-life of nifedipine is about 2 hours when administered as conventional capsules, and about 7 hours when administered as coat-core (CC) extended-release tablets.
The drug is extensively metabolized in the liver (to highly water-soluble, inactive metabolites) by the cytochrome P-450 microsomal enzyme system, including CYP3A. Approximately 60-80% of an oral dose of nifedipine is excreted as metabolites in the urine, with only traces (less than 0.1%) of an oral dose being excreted in urine as unchanged drug. The remainder of a dose is excreted in the feces as metabolites, possibly via biliary elimination.
Nifedipine appears to be negligibly removed by hemodialysis or hemoperfusion. The elimination half-life of nifedipine has been reported to increase to 7 hours in patients with liver cirrhosis; oral bioavailability of the drug also is increased in such patients.
USES: This medication is used to prevent chest pain (angina). It may help to increase your ability to exercise and decrease how often you may get angina attacks. It should not be used to treat attacks of chest pain when they occur.
Use other medications (such as sublingual nitroglycerin) to relieve attacks of chest pain as directed by your doctor. Consult your doctor or pharmacist for details. Nifedipine belongs to a class of drugs known as calcium channel blockers.
It works by relaxing blood vessels so blood can flow more easily. Older adults should discuss the risks and benefits of this medication with their doctor or pharmacist, as well as other possibly safer forms of nifedipine (such as the long-acting tablets).
Generic name: nifedipine
Pronunciation: (nye-FED-i-peen)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Procardia
Indications
The following indications are listed for Procardia:
- Prevention Of Anginal Pain Associated With Coronary Artery Disease
- Prevention Of Anginal Pain Associated With Vasospastic Angina
Also known as: Prevention Of Anginal Pain Associated With Angina Inversa, Prevention Of Anginal Pain Associated With Cad, Prevention Of Anginal Pain Associated With Prinzmetal Angina, Prevention Of Anginal Pain Associated With Variant Angina.
Dosing
No dosing information is available for this tab.
Nifedipine is administered orally as short-acting (conventional, immediate-release) capsules or as extended-release tablet formulations; the tablet formulations are commercially available as a gastrointestinal therapeutic system (GITS) or coat-core (CC) tablet.
Nifedipine has been administered sublingually+ or intrabuccally+ for rapid reduction of blood pressure; however, it is no longer acceptable to use short-acting (conventional, immediate-release capsules) nifedipine for this use.
Whenever extended-release tablets of nifedipine are dispensed, care should be taken to ensure that the extended-release dosage form has been prescribed.
The manufacturers recommend that dosage of nifedipine be decreased gradually with close clinical supervision when discontinuance of the drug is required.
Concomitant oral administration of 1,4-dihydropyridine-derivative calcium-channel blocking agents (e.g., nifedipine) with grapefruit juice usually should be avoided since potentially clinically important increases in bioavailability may result.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Metabolism of nifedipine is mediated by the cytochrome P-450 (CYP) microsomal enzyme system (principally the 3A isoenzyme) and concomitant use of nifedipine with inhibitors or inducers of CYP3A may be associated with altered nifedipine exposure resulting in favorable or unfavorable effects. In addition, in vitro and in vivo data indicate that nifedipine may inhibit metabolism of drugs that are substrates of CYP3A, thereby increasing exposure to other drugs. Nifedipine does not appear likely to affect the metabolism of CYP2D6 substrates.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Hypersensitivity to nifedipine or any component of the formulation.
*Cardiogenic shock.
*Concomitant administration with strong cytochrome P-450 (CYP) inducers (e.g., rifampin).
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects reported with nifedipine in clinical studies were peripheral edema, dizziness/lightheadedness, flushing/heat sensation, headache, tremor, nervousness, mood changes, weakness, fatigue/asthenia, muscle cramps, nausea, heartburn, constipation, palpitation, dyspnea, cough, wheezing, nasal congestion, and sore throat.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Although safety and efficacy remain to be fully established in pediatric patients younger than 18 years of age, some experts have recommended pediatric dosages for hypertension based on clinical experience.
There are no adequate and well-controlled studies using nifedipine in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.
Nifedipine has been shown to be teratogenic in rats and rabbits. Digital anomalies similar to those reported with phenytoin also have been reported in the offspring of animals receiving other dihydropyridines; these anomalies may occur secondary to compromised uterine blood flow. Nifedipine administration in rats, mice, rabbits, and monkeys also has been associated with a variety of other embryotoxic, placentotoxic, and fetotoxic effects, including stunted fetuses (rats, mice, and rabbits), rib deformities (mice), cleft palate (mice), small placentas and underdeveloped chorionic villi (monkeys), embryonic and fetal deaths (rats, mice, and rabbits), and prolonged pregnancy/decreased neonatal survival (rats; not evaluated in other species). The dosages (on a mg/kg basis) of nifedipine associated with teratogenic, embryotoxic, or fetotoxic effects in animals were higher (5-50 times) than the maximum recommended human dosage (120 mg daily); however, such dosages were within one order of magnitude of the maximum recommended human dosage. The dosages of nifedipine associated with placentotoxic effects in monkeys were equivalent to or lower than the maximum recommended human dosage on a mg/m2 basis.
From the clinical evidence available, a specific prenatal risk has not been identified. However, an increase in perinatal asphyxia, caesarean delivery, prematurity, and intrauterine growth retardation has been reported.
Monitor blood pressure carefully when administering nifedipine in combination with IV magnesium sulfate in pregnant women due to the possibility of an excessive fall in blood pressure, which could harm the mother and fetus.
Nifedipine is distributed into milk. In one lactating woman who received 10, 20, and 30 mg of the drug every 8 hours as conventional capsules, peak milk concentrations of nifedipine occurred within 1 hour after a dose and ranged from about 13-53 ng/mL; the drug generally was not detectable during the hour prior to a dose. Because of the potential for serious adverse reactions to nifedipine in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
Increased nifedipine exposure has been observed in pharmacokinetic studies in small numbers of geriatric patients; however, clinical experience generally has not revealed age-related differences in response or tolerance. The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in geriatric patients should be considered; initiate therapy at the low end of the dosage range and adjust dosage as necessary based on patient response.
Although a prolonged elimination half-life and an increase in peak plasma concentration and AUC have been observed in pharmacokinetic studies in small numbers of patients, clinical studies of nifedipine did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger adults. While other clinical experience generally has not revealed age-related differences in response or tolerance, drug dosage generally should be titrated carefully in geriatric patients, usually initiating therapy at the low end of the dosage range and adjusting dosage as necessary based on patient response. The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in geriatric patients also should be considered.
Following oral administration of coat-core (CC) extended-release nifedipine tablets in healthy geriatric individuals (older than 60 years of age), the mean peak plasma concentrations and average plasma concentrations of nifedipine were 36 and 70% higher, respectively, compared with those observed in younger adults.
ICD codes
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Last reviewed · Source: First Databank (FDB) drug data
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