Extended Release Tablets
For Oral Use
DESCRIPTION
CLINICAL PHARMACOLOGY
INDICATIONS AND USAGE
CONTRAINDICATIONS
WARNINGS
PRECAUTIONS
ADVERSE REACTIONS
OVERDOSAGE
DOSAGE AND ADMINISTRATION
HOW SUPPLIED
Nifedipine is a drug belonging to a class of pharmacological agents known as the calcium channel blockers.
Nifedipine is 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2 ,6-dimethyl-4-(2-nitrophenyl)-, dimethyl ester,
C17H18N2O6 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 XL is a trademark for Nifedipine GITS. Nifedipine GITS
(Gastrointestinal Therapeutic System) Tablet is formulated as a once-a-day controlled-release tablet for oral
administration designed to deliver 30, 60, or 90 mg of nifedipine.
Inert ingredients in the formulations are: cellulose acetate; hydroxypropyl cellulose; hydroxypropyl
methylcellulose; magnesium stearate; polyethylene glycol; polyethylene oxide; red ferric oxide; sodium chloride;
titanium dioxide.
System Components and Performance
PROCARDIA XL Extended Release Tablet is similar in appearance to a conventional tablet, It consists,
however, of a semipermeable membrane surrounding an osmotically active drug core. The core itself is divided
into two layers: an “active” layer containing the drug, and a “push” layer containing pharmacologically inert (but
osmotically active) components. As water from the gastrointestinal tract enters the tablet, pressure increases in
the osmotic layer and”pushes” against the drug layer, releasing drug through the precision laser-drilled tablet
orifice in the active layer.
PROCARDIA XL Extended Release Tablet is designed to provide nifedipine at an approximately constant rate
over 24 hours. This controlled rate of drug delivery into the gastrointestinal lumen is independent of pH or
gastrointestinal motility. PROCARDIA XL depends for its action on the existence of an osmotic gradient
between the contents of the bi-layer core and fluid in the GI tract. Drug delivery is essentially constant as long as
the osmotic gradient remains constant, and then gradually falls to zero. Upon swallowing, the biologically inert
components of the tablet remain intact during GI transit and are eliminated in the feces as an insoluble shell.
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. Nifedipine selectively inhibits calcium ion influx across the cell
membrane of cardiac muscle and vascular smooth muscle without altering serum calcium concentrations.
Mechanism of Action
A) Angina
The precise mechanisms by which inhibition of calcium influx relieves angina has not been fully determined, but
includes at least the following two mechanisms:
- Relaxation and Prevention of Coronary Artery Spasm
Nifedipine dilates the main coronary arteries and coronary arterioles, both in normal and ischemic regions, and is a potent inhibitor of coronary artery spasm,
whether spontaneous or ergonovine-induced. This property increases myocardial oxygen delivery in patients
with coronary artery spasm, and is responsible for the effectiveness of nifedipine in vasospastic (Prinzmetal’s or
variant) angina. Whether this effect plays any role in classical angina is not clear, but studies of exercise
tolerance have not shown an increase in the maximum exercise rate-pressure product, a widely accepted measure
of oxygen utilization. This suggests that, in general, relief of spasm or dilation of coronary arteries is not an
important factor in classical angina.
- Reduction of Oxygen Utilization
Nifedipine regularly reduces arterial pressure at rest and at a given level of exercise by dilating peripheral
arterioles and reducing the total peripheral vascular resistance (afterload) against which the heart works. This
unloading of the heart reduces myocardial energy consumption and oxygen requirements, and probably accounts
for the effectiveness of nifedipine in chronic stable angina.
B) Hypertension
The mechanism by which nifedipine reduces arterial blood pressure involves peripheral arterial vasodilatation and
the resulting reduction in peripheral vascular resistance. The increased peripheral vascular resistance that is 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.
Pharmacokinetics and Metabolism
Nifedipine is completely absorbed after oral administration. Plasma drug concentrations rise at a gradual,
controlled rate after a PROCARDIA XL Extended Release Tablet dose and reach a plateau at approximately six
hours after the first dose. For subsequent doses, relatively constant plasma concentrations at this plateau are
maintained with minimal fluctuations over the 24 hour dosing interval. About a four-fold higher fluctuation
index (ratio of peak to trough plasma concentration) was observed with the conventional immediate release
Procardiaâ capsule at t.i.d. dosing than with once daily PROCARDIA XL Extended Release Tablet. At steady-
state the bioavailability of the PROCARDIA XL Extended Release Tablet is 86% relative to Procardia capsules.
Administration of the PROCARDIA XL Extended Release Tablet in the presence of food slightly alters the early
rate of drug absorption, but does not influence the extent of drug bioavailability. Markedly reduced GI retention
time over prolonged periods (i.e., short bowel syndrome), however, may influence the pharmacokinetic profile of
the drug which could potentially result in lower plasma concentrations. Pharmacokinetics of PROCARDIA XL
Extended Release Tablets are linear over the dose range of 30 to 180 mg in that plasma drug concentrations are
proportional to dose administered. There was no evidence of dose dumping either in the presence or absence of
food for over 150 subjects in pharmacokinetic studies.
Nifedipine is extensively metabolized to highly water-soluble, inactive metabolites accounting for 60 to 80% of
the dose excreted in the urine. The elimination half-life of nifedipine is approximately two hours. Only traces
(less than 0.1% of the dose) of 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. Thus, the pharmacokinetics of nifedipine
are not significantly influenced by the degree of renal impairment. Patients in hemodialysis or chronic ambulatory
peritoneal dialysis have not reported significantly altered pharmacokinetics of nifedipine. 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.
Hemodynamics
Like other slow-channel blockers, nifedipine exerts a negative inotropic effect on isolated myocardial tissue. This
is rarely, it 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 tall in systolic and diastolic pressures,
usually minimal in normotensive volunteers (less than 5-10 mm Hg systolic), but sometimes larger With
PROCARDIA XL Extended Release Tablets, these decreases in blood pressure are not accompanied by any
significant change in heart rate. Hemodynamic studies 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 tilling 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 has had no tendency to prolong atrioventricular conduction or sinus node recovery time, or to
slow sinus rate.
- Vasospastic Angina
PROCARDIA XL is indicated for the management of vasospastic angina confirmed by any of the following
criteria: 1) classical pattern of angina at rest accompanied by ST segment elevation, 2) angina or coronary artery
spasm provoked by ergonovine, or 3) angiographically demonstrated coronary artery spasm. In those patients
who have had angiography, the presence of significant fixed obstructive disease is not incompatible with the
diagnosis of vasospastic angina, provided that the above criteria are satisfied. PROCARDIA XL may also be
used where the clinical presentation suggests a possible vasospastic component but where vasospasm has not
been confirmed, e.g., where pain has a variable threshold on exertion or in unstable angina where
electrocardiographic findings are compatible with intermittent vasospasm, or when angina is refractory to nitrates
and/or adequate doses of beta blockers. - Chronic Stable Angina
(Classical Effort-Associated Angina)
PROCARDIA XL 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) 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 is incomplete.
Controlled studies in small numbers of patients suggest concomitant use of 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
WARNINGS.) - Hypertension
PROCARDIA XL is indicated for the treatment of hypertension. It may be used alone or in combination with
other antihypertensive agents.
Known hypersensitivity reaction to nifedipine.
Excessive Hypotension
Although in most angina 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 on
concomitant beta blockers.
Severe hypotension and/or increased fluid volume requirements have been reported in patients receiving
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 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 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 nifedipine
to be washed out of the body prior to surgery.
The following information should be taken into account in those patients who are being treated for hypertension
as well as angina:
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 on starting
nifedipine or at the time of dosage increase. The mechanism of this effect is not established.
Beta Blocker Withdrawal
It is important to taper beta blockers if possible, rather than stopping them 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 receiving a beta blocker, have developed heart failure after beginning nifedipine. Patients
with tight aortic stenosis may be at risk for such an event, as the unloading effect of nifedipine would be expected
to be of less benefit to those patients, owing to t heir fixed impedance to flow across the aortic valve.
General-Hypotension: Because nifedipine decreases peripheral vascular resistance, careful monitoring of blood pressure during the initial administration and titrat
ion of nifedipine is suggested. Close observation is especially
recommended for patients already taking medications that are known to lower blood pressure. (See WARNINGS.)
Peripheral Edema: Mild to moderate peripheral edema occurs in a dose dependent manner with an incidence
ranging from approximately 10% to about 30% at the highest dose studied (180 mg). It is a localized phenomenon thought to be associated with vasodilation of dependent arterioles and small blood vessels and not due to left ventricular dysfunction or gener
alized fluid retention. With patients whose angina or hypertension is complicated by congestive heart failure, care should be taken to differentiate this peripheral edema from the
effects of increasing left ventricular dysfunction.
Other: As with any other non-deformable material, caution should be used when administering PROCARDIA
XL in patients with preexisting severe gastrointestinal narrowing (pathologic or iatrogenic). There have been
rare reports of obstructive symptoms in patients with known strictures in association with the ingestion of
PROCARDIA XL.
Information for Patients: PROCARDIA XL Extended Release Tablets should be swallowed whole. Do not
chew, divide or crush tablets. Do not be concerned if you occasionally notice in your stool something that looks
like a tablet. In PROCARDIA XL, the medication is contained within a nonabsorbable shell that has been
specially designed to slowly release the drug for your body to absorb. When this process is completed, the empty
tablet is eliminated from your body.
Laboratory Tests: Rare, usually transient, but occasionally significant elevations of enzymes such as alkaline
phosphatase. CPK, LDH, SGOT, and SGPT have been noted. The relationship to 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. A small (5.4%) increase in
mean alkaline phosphatase was noted in patients treated with PROCARDIA XL. This was an isolated finding
not associated with clinical symptoms and it rarely resulted in values which fell outside the normal range. Rare
instances of allergic hepatitis have been reported. In controlled studies, PROCARDIA XL did not adversely
affect serum uric acid, glucose, or cholesterol. Serum potassium was unchanged in patients receiving
PROCARDIA XL in the absence of concomitant diuretic therapy, and slightly decreased in patients receiving
concomitant diuretics.
Nifedipine, like other calcium channel blockers, decreases platelet aggregation in vitro. Limited clinical studies have demonstrated a moderate but statistically significant decrease in platelet aggregation and increase in
bleeding time in some 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
nifedipine administration and positivity of this laboratory test, including hemolysis, could not be determined.
Although 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 preexisting chronic renal insufficiency. The relationship to nifedipine therapy is uncertain in most
cases but probable in some.
Drug Interactions: Beta-adrenergic blocking agent (see INDICATIONS and WARNINGS.) Experience in over
1400 patients with Procardia capsules in a noncomparative clinical trial has shown that concomitant
administration of nifedipine and betablocking agents is usually well tolerated but there have been occasional
literature reports suggesting that the combination may increase the likelihood of congestive heart failure, severe
hypotension, or exacerbation of angina.
Long Acting Nitrates: Nifedipine may be safely co-administered with nitrates, but there have been no controlled
studies to evaluate the antianginal effectiveness of this combination.
Digitalis: Administration of nifedipine with digoxin increased digoxin levels in nine of twelve normal volunteers.
The average increase was 45%. Another investigator found no increase in digoxin levels in thirteen patients with
coronary artery disease. In an uncontrolled study of over two hundred patients with congestive heart failure
during which digoxin blood levels were not measured, digitalis toxicity was not observed. Since there have been
isolated reports of patients with elevated digoxin levels, it is recommended that digoxin levels be monitored when
initiating, adjusting, and discontinuing nifedipine to avoid possible over- or under-digitalization.
Coumarin Anticoagulants: There have been rare reports of increased prothrombin time in patients taking
cournarin anticoagulants to whom nifedipine was administered. However, the relationship to nifedipine therapy
is uncertain.
Cimetidine: A study in six healthy volunteers has shown a significant increase in peak nifedipine plasma levels
(80%) and area-under-the-curve (74%), after a one week course of cimetidine at 1000 mg per day and nifedipine
at 40 mg per day. Ranitidine produced smaller, non-significant increases. The effect may be mediated by the
known inhibition of cimetidine on hepatic cytochrome P-450, the enzyme system probably responsible for the
first-pass metabolism of nifedipine. If nifedipine therapy is initiated in a patient currently receiving cimetidine,
cautious titration is advised.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Nifedipine was administered orally to rats for two years and was not shown to be carcinogenic. When given to rats prior to mating, nifedipine caused reduced fertility at a dose approx
imately 30 times the maximum recommended human dose. There is a literature report of reversible reduction in the ability of human sperm obtained from a limited number of infertile men taking recommended doses of nifedipine to bind to and fertilize an ovu
m in vitro. In vivo mutagenicity studies were negative.
Pregnancy: Pregnancy Category C. Nifedipine has been shown to be teratogenic in rats when given in doses 30
times the maximum recommended human dose. Nifedipine was embryotoxic (increased fetal resorptions, decreased fetal weight, increased stunted forms, increased fetal deaths. decreased neonatal survival) in rats, mice, and rabbits at doses of from 3 to 10 t
imes the maximum recommended human dose. In pregnant monkeys, doses 2/3 and twice the maximum recommended human dose resulted in small placentas and underdeveloped chorionic villi. In rats, doses three times maximum human dose and higher caused prolonga
tion of pregnancy There are no
adequate and well controlled studies in pregnant women. PROCARDIA XL Extended Release Tablets should be
used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Over 1000 patients from both controlled and open trials with PROCARDIA XL Extended Release Tablets in
hypertension and angina were included in the evaluation of adverse experiences. All side effects reported during
PROCARDIA XL Extended Release Tablet therapy were tabulated independent of their causal relation to
medication. The most common side effect reported with PROCARDIA XL was edema which was dose related
and ranged in frequency from approximately 10% to about 30% at the highest dose studied (180 mg). Other
common adverse experiences reported in placebo-controlled trials include:
PROCARDIA XL (%) Placebo (%) Adverse Effect (N=707) (N=266) Headache 15.8 9.8 Fatigue 5.9 4.1 Dizziness 4.1 4.5 Constipation 3.3 2.3 Nausea 3.3 1.9
Of these, only edema and headache were more common in PROCARDIA XL patients than placebo patients.
The following adverse reactions occurred with an incidence of less than 3.0%. With the exception of leg cramps,
the incidence of these side effects was similar to that of placebo alone.
-
Body as a Whole/Systemtic: asthenia, flushing, pain
Cardiovascular: palpitations
Central Nervous System: insomnia, nervousness, paresthesia, somnolence
Dermatologic: pruritus, rash
Gastrointestinal: abdominal pain, diarrhea, dry mouth, dyspepsia, flatulence
Musculoskeletal: arthralgia, leg cramps
Respiratory: chest pain (nonspecific), dyspnea
Urogenital: impotence, polyuria
Other adverse reactions were reported sporadically with an incidence of 1.0% or less . These include:
-
Body as a Whole/Systemic: face edema, fever, hot flashes, malaise, periorbital edema, rigors
Cardiovascular: arrhythmia, hypotension, increased angina, tachycardia, syncope
Central Nervous System: anxiety, ataxia, decreased libido, depression, hypertonia, hypoesthesia, migraine,
paroniria, tremor, vertigo
Dermatologic: alopecia, increased sweating, urticaria, purpura
Gastrointestinal: eructation, gastroesophageal reflux, gum hyperplasia, melena, vomiting, weight increase
Musculoskeletal: back pain, gout, myalgias
Respiratory: coughing, epistaxis, upper respiratory tract infection, respiratory disorder, sinusitis
Special Senses: abnormal lacrimation, abnormal vision, taste perversion, tinnitus
Urogenital/Reproductive: breast pain, dysuria, hernaturia, nocturia
Adverse experiences which occurred in less than 1 in 1000 patients cannot be distinguished from concurrent
disease states or medications.
The following adverse experiences, reported in less than 1% of patients, occurred under conditions (e.g. open trials, marketing experience) where a causal relationship is uncertain: gastrointestinal irritation, gastrointestinal bleeding.
In multiple-dose U.S. and foreign controlled studies with nifedipine capsules 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.
PROCARDIA CAPSULES(%) Placebo (%) Adverse Effect (N=226) (N=235) Dizziness, lightheadedness, giddiness 27 15 Flushing, heat sensation 25 8 Headache 23 20 Weakness 12 10 Nausea, heartburn 11 8 Muscle cramps, tremor 8 3 Peripheral edema 7 1 Nervousness, mood changes 7 4 Palpitation 7 5 Dyspnea, cough, wheezing 6 3 Nasal congestion, sore throat 6 8
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 relatively common adverse events were similar in nature to those seen with PROCARDIA XL.
In addition, more serious adverse events were observed, not readily distinguishable from the natural history of
the disease in these patients. It remains possible, however, that some or many of these events were drug related.
Myocardial infarction occurred in about 4% of patients and congestive heart failure or pulmonary edema in about
2%. Ventricular arrhythmias or conduction disturbances each occurred in fewer than 0.5% of patients.
In a subgroup of over 1000 patients receiving PROCARDIA with concomitant beta blocker therapy, the pattern
and incidence of adverse experiences was not different from that of the entire group of PROCARDIA
(nifedipine) treated patients (See PRECAUTIONS )
In a subgroup of approximately 250 patients with a diagnosis of congestive heart failure is well as angina,
dizziness or lightheadedness, peripheral edema, headache or flushing each occurred in one in eight patients.
Hypotension occurred in about one in 20 patients. Syncope occurred in approximately one patient in 250.
Myocardial infarction or symptoms of congestive heart failure each occurred in about one patient in 15. Atrial or
ventricular dysrhythmias each occurred in about one patient in 150.
In post-marketing experience, there have been rare reports of exfoliative dermatifis caused by nifedipine.
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, 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.
There has been one reported case of massive overdosage with PROCARDIA XL Extended Release Tablets. The
main effects of ingestion of approximately 4800 mg of PROCARDIA XL 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. Electrolyte 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 Procardia capsules in a depressed anginal patient also 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 Procardia. 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.
PROCARDIA XL® Extended Release Tablets are supplied as 30 mg, 60 mg and 90 mg round biconvex, rose-pink, film-coated tablets in:
Bottles of 100: 30 mg (NDC 0069-2650-66) (NDC 59012-265-66) 60 mg (NDC 0069-2660-66) (NDC 59012-266-66) 90 mg (NDC 0069-2670-66) (NDC 59012-267-66) Bottles of 300: 30 mg (NDC 0069-2650-72) (NDC 59012-265-72) 60 mg (NDC 0069-2660-72) (NDC 59012-266-72) Bottles of 5000:30 mg (NDC 0069-2650-94) (NDC 59012-265-94) 60 mg (NDC 0069-2660-94) (NDC 59012-266-94) Unit dose packages of 100:30 mg (NDC 0069-2650-41) (NDC 59012-265-41) 60 mg (NDC 0069-2660-41) (NDC 59012-266-41) 90 mg (NDC 0069-2670-41) (NDC 59012-267-41)
Store below 86ºF (30ºC).
Protect from moisture and humidity
© 1994 PFIZER INC.
