Procardia Information
Procardia (Nifedipine) Description
Procardia (Nifedipine) is an antianginal drug belonging to a class of pharmacological agents, the calcium channel blockers. Nifedipine is 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-, dimethyl ester, CHNO, and has the structural formula:
Nifedipine is a yellow crystalline substance, practically insoluble in water but soluble in ethanol. It has a molecular weight of 346.3. Procardia (Nifedipine) capsules are formulated as soft gelatin capsules for oral administration, each containing 10 mg nifedipine.
Inert ingredients in the formulation are: glycerin; peppermint oil; polyethylene glycol; soft gelatin capsules (which contain Yellow 6, and may contain Red Ferric Oxide and other inert ingredients); and water. The 10 mg capsules also contain saccharin sodium.
Procardia (Nifedipine) Clinical Pharmacology
Procardia (Nifedipine) is a calcium ion influx inhibitor (slow-channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac muscle and smooth muscle. 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. Procardia (Nifedipine) selectively inhibits calcium ion influx across the cell membrane of cardiac muscle and vascular smooth muscle without changing serum calcium concentrations.
Procardia (Nifedipine) is rapidly and fully absorbed after oral administration. The drug is detectable in serum 10 minutes after oral administration, and peak blood levels occur in approximately 30 minutes. Bioavailability is proportional to dose from 10 to 30 mg; half-life does not change significantly with dose. There is little difference in relative bioavailability when Procardia (Nifedipine) capsules are given orally and either swallowed whole, bitten and swallowed, or bitten and held sublingually. However, biting through the capsule prior to swallowing does result in slightly earlier plasma concentrations (27 ng/mL 10 minutes after 10 mg) than if capsules are swallowed intact. Procardia (Nifedipine) is highly bound by serum proteins. Procardia (Nifedipine) is extensively converted to inactive metabolites and approximately 80 percent of Procardia (Nifedipine) and metabolites are eliminated via the kidneys. The half-life of nifedipine in plasma is approximately two hours. Since hepatic biotransformation is the predominant route for the disposition of nifedipine, the pharmacokinetics may be altered in patients with chronic liver disease. Patients with hepatic impairment (liver cirrhosis) have a longer disposition half-life and higher bioavailability of nifedipine than healthy volunteers. The degree of serum protein binding of nifedipine is high (92–98%). Protein binding may be greatly reduced in patients with renal or hepatic impairment.
In healthy subjects, the elimination half-life of a BID sustained release nifedipine formulation [that was neither Procardia (Nifedipine) capsules nor Procardia (Nifedipine) XL (nifedipine) extended release tablets] 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) following intravenous administration.
Co-administration of nifedipine with grapefruit juice resulted in approximately a 2-fold increase in nifedipine AUC and Cmax with no change in half-life. The increased plasma concentrations are most likely due to inhibition of CYP 3A4 related first-pass metabolism.
Procardia (Nifedipine) Indications And Usage
Procardia (Nifedipine) is indicated for the management of chronic stable angina (effort-associated angina) without evidence of vasospasm in patients who remain symptomatic despite adequate doses of beta blockers and/or organic nitrates or who cannot tolerate those agents.
In chronic stable angina (effort-associated angina), Procardia (Nifedipine) has been effective in controlled trials of up to eight weeks duration in reducing angina frequency and increasing exercise tolerance, but confirmation of sustained effectiveness and evaluation of long-term safety in these patients are incomplete.
Controlled studies in small numbers of patients suggest concomitant use of Procardia (Nifedipine) and beta-blocking agents may be beneficial in patients with chronic stable angina, but available information is not sufficient to predict with confidence the effects of concurrent treatment, especially in patients with compromised left ventricular function or cardiac conduction abnormalities. When introducing such concomitant therapy, care must be taken to monitor blood pressure closely since severe hypotension can occur from the combined effects of the drugs. (See .)
Procardia (Nifedipine) Contraindications
Known hypersensitivity reaction to Procardia (Nifedipine) .
Procardia (Nifedipine) Warnings
Although, in most patients, the hypotensive effect of Procardia (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. Although patients have rarely experienced excessive hypotension on Procardia (Nifedipine) alone, this may be more common in patients on concomitant beta blocker therapy. Although not approved for this purpose, Procardia (Nifedipine) and other immediate-release nifedipine capsules have been used (orally and sublingually) for acute reduction of blood pressure. Several well-documented reports describe cases of profound hypotension, myocardial infarction, and death when immediate-release nifedipine was used in this way.
Severe hypotension and/or increased fluid volume requirements have been reported in patients receiving Procardia (Nifedipine) together with a beta-blocking agent 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 Procardia (Nifedipine) and a beta blocker, but the possibility that it may occur with Procardia (Nifedipine) alone, with low doses of fentanyl, in other surgical procedures, or with other narcotic analgesics cannot be ruled out. In Procardia (Nifedipine) treated patients where surgery using high dose fentanyl anesthesia 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 Procardia (Nifedipine) to be washed out of the body prior to surgery.
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 on starting Procardia (Nifedipine) or at the time of dosage increase. The mechanism of this effect is not established.
Several well-controlled, randomized trials studied the use of immediate-release nifedipine in patients who had just sustained myocardial infarctions. In none of these trials did immediate-release nifedipine appear to provide any benefit. In some of the trials, patients who received immediate-release nifedipine had significantly worse outcomes than patients who received placebo.
Procardia (Nifedipine) Precautions
Rare, usually transient, but occasionally significant elevations of enzymes such as alkaline phosphatase, CPK, LDH, SGOT, and SGPT have been noted. The relationship to Procardia (Nifedipine) therapy is uncertain in most cases, but probable in some. These laboratory abnormalities have rarely been associated with clinical symptoms; however, cholestasis with or without jaundice has been reported. Rare instances of allergic hepatitis have been reported.
Procardia (Nifedipine) , like other calcium channel blockers, decreases platelet aggregation . Limited clinical studies have demonstrated a moderate but statistically significant decrease in platelet aggregation and an increase in bleeding time in some Procardia (Nifedipine) patients. This is thought to be a function of inhibition of calcium transport across the platelet membrane. No clinical significance for these findings has been demonstrated.
Positive direct Coombs Test with/without hemolytic anemia has been reported but a causal relationship between Procardia (Nifedipine) administration and positivity of this laboratory test, including hemolysis, could not be determined.
Although Procardia (Nifedipine) has been used safely in patients with renal dysfunction and has been reported to exert a beneficial effect, in certain cases, rare, reversible elevations in BUN and serum creatinine have been reported in patients with pre-existing chronic renal insufficiency. The relationship to Procardia (Nifedipine) therapy is uncertain in most cases but probable in some.
Procardia (Nifedipine) Adverse Reactions
In multiple-dose United States and foreign controlled studies in which adverse reactions were reported spontaneously, adverse effects were frequent but generally not serious and rarely required discontinuation of therapy or dosage adjustment. Most were expected consequences of the vasodilator effects of Procardia (Nifedipine) .
There is also a large uncontrolled experience in over 2100 patients in the United States. Most of the patients had vasospastic or resistant angina pectoris, and about half had concomitant treatment with beta-adrenergic blocking agents. The most common adverse events were:
Procardia (Nifedipine) Overdosage
Experience with nifedipine overdosage is limited. Generally, overdosage with nifedipine leading to pronounced hypotension calls for active cardiovascular support including monitoring of cardiovascular and respiratory function, elevation of extremities, and judicious use of calcium infusion, pressor agents, and fluids. 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.
Procardia (Nifedipine) Dosage And Administration
Therapy should be initiated with the 10 mg capsule. The starting dose is one 10 mg capsule, swallowed whole, 3 times/day. The usual effective dose range is 10–20 mg three times daily. Some patients, especially those with evidence of coronary artery spasm, respond only to higher doses, more frequent administration, or both. In such patients, doses of 20–30 mg three or four times daily may be effective. Doses above 120 mg daily are rarely necessary. More than 180 mg per day is not recommended.
In most cases, Procardia (Nifedipine) titration should proceed over a 7–14 day period so that the physician can assess the response to each dose level and monitor the blood pressure before proceeding to higher doses.
If symptoms so warrant, titration may proceed more rapidly provided that the patient is assessed frequently. Based on the patient's physical activity level, attack frequency, and sublingual nitroglycerin consumption, the dose of Procardia (Nifedipine) may be increased from 10 mg t.i.d. to 20 mg t.i.d. and then to 30 mg t.i.d. over a three-day period.
In hospitalized patients under close observation, the dose may be increased in 10 mg increments over four- to six-hour periods as required to control pain and arrhythmias due to ischemia. A single dose should rarely exceed 30 mg.
Co-administration of nifedipine with grapefruit juice is to be avoided (see and ).
No "rebound effect" has been observed upon discontinuation of Procardia (Nifedipine) . However, if discontinuation of Procardia (Nifedipine) is necessary, sound clinical practice suggests that the dosage should be decreased gradually with close physician supervision.
Procardia (Nifedipine) How Supplied
Procardia (Nifedipine) soft gelatin capsules are supplied in:
Bottles of 100: 10 mg (NDC 0069-2600-66)
Procardia (Nifedipine)
Procardia (Nifedipine) Principal Display Panel - Mg Bottle Label
