Procardia

You should not use nifedipine if you are allergic to it.

Before taking nifedipine, tell your doctor if you have kidney or liver disease, a blockage in your digestive tract (stomach or intestines), a history of stomach surgery, coronary artery disease, underactive thyroid, diabetes, or congestive heart failure.

If you need surgery, tell the surgeon ahead of time that you are using nifedipine. You may need to stop using the medicine for a short time.

Many drugs can interact with nifedipine. Tell your doctor about all other medications you use.

Do not stop taking nifedipine without first talking to your doctor, even if you feel fine. Stopping suddenly may make your condition worse. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Nifedipine is a prescription medication used to treat chest pain.

The extended release form of nifedipine, is a prescription medication used to treat chest pain and high blood pressure.

These medications may be prescribed for other uses. Ask your doctor or pharmacist for more information.

• Pfizer Laboratories Div Pfizer Inc.

Take nifedipine exactly as prescribed.

This medication comes in an immediate release capsule form and is taken 3 or 4 times a day, with or without food. Swallow whole, do not chew or crush the capsule or its contents.

This medication also comes in an extended release tablet form and is taken once a day, with or without food. Do not chew or swallow these tablets. These tablets are made with a non-absorbable shell that may be passed into the stools. This is an expected occurrence.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of nifedipine at the same time.

If you take too much nifedipine, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

You should not use nifedipine if you have severe coronary artery disease, or if you have had a heart attack within the past 2 weeks.

You should not use this medicine if you are allergic to nifedipine, if you have severe coronary artery disease, or if you have had a heart attack within the past 2 weeks.

To make sure nifedipine is safe for you, tell your doctor if you have:

• severe COPD (chronic obstructive pulmonary disease);

• kidney disease;

• congestive heart failure; or

• if you take other medications, especially an antibiotic or antifungal medicine, an antidepressant, heart or blood pressure medicine, or drugs to treat HIV/AIDS or hepatitis C.

It is not known whether nifedipine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Nifedipine can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

The nifedipine extended-release tablet may contain lactose. Talk to your doctor before using this form of nifedipine if you have galactose intolerance, or severe problems with lactose (milk sugar).

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Very bad dizziness or passing out.
• Chest pain that is new or worse.
• A heartbeat that does not feel normal.
• Mood changes.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• Muscle pain or cramping.
• Shakiness.
• Very bad belly pain.
• Very hard stools (constipation).
• Black, tarry, or bloody stools.
• Throwing up blood or throw up that looks like coffee grounds.

General

Because Procardia decreases peripheral vascular resistance, careful monitoring of blood pressure during the initial administration and titration of Procardia is suggested. Close observation is especially recommended for patients already taking medications that are known to lower blood pressure. (See WARNINGS.)

Mild to moderate peripheral edema, typically associated with arterial vasodilation and not due to left ventricular dysfunction, occurs in about one in ten patients treated with Procardia (nifedipine). This edema occurs primarily in the lower extremities and usually responds to diuretic therapy. With patients whose angina is complicated by congestive heart failure, care should be taken to differentiate this peripheral edema from the effects of increasing left ventricular dysfunction.

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 Procardia 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, 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 an increase in bleeding time in some Procardia 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 administration and positivity of this laboratory test, including hemolysis, could not be determined.

Although Procardia 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 therapy is uncertain in most cases but probable in some.

Drug Interactions

(See INDICATIONS AND USAGE and WARNINGS.) Experience in over 1400 patients in a non-comparative clinical trial has shown that concomitant administration of Procardia and beta-blocking 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.

Procardia may be safely co-administered with nitrates, but there have been no controlled studies to evaluate the antianginal effectiveness of this combination.

Since there have been isolated reports of patients with elevated digoxin levels, and there is a possible interaction between digoxin and nifedipine, it is recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing nifedipine to avoid possible over- or under-digitalization.

There have been rare reports of an interaction between quinidine and nifedipine (with a decreased plasma level of quinidine).

There have been rare reports of increased prothrombin time in patients taking coumarin anticoagulants to whom Procardia was administered. However, the relationship to Procardia therapy is uncertain.

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.

Other Interactions

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. Co-administration of nifedipine with grapefruit juice is to be avoided.

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 approximately 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 ovum in vitro. In vivo mutagenicity studies were negative.

Pregnancy

Nifedipine has been shown to produce teratogenic findings in rats and rabbits, including digital anomalies similar to those reported for phenytoin. Digital anomalies have been reported to occur with other members of the dihydropyridine class and are possibly a result of compromised uterine blood flow. Nifedipine administration was associated with a variety of embryotoxic, placentotoxic, and fetotoxic effects, including stunted fetuses (rats, mice, rabbits), rib deformities (mice), cleft palate (mice), small placentas and underdeveloped chorionic villi (monkeys), embryonic and fetal deaths (rats, mice, rabbits), and prolonged pregnancy/decreased neonatal survival (rats; not evaluated in other species). On a mg/kg basis, all of the doses associated with the teratogenic embryotoxic or fetotoxic effects in animals were higher (3.5 to 42 times) than the maximum recommended human dose of 120 mg/day. On a mg/m2 basis, some doses were higher and some were lower than the maximum recommended human dose but all are within an order of magnitude of it. The doses associated with placentotoxic effects in monkeys were equivalent to or lower than the maximum recommended human dose on a mg/m2 basis.

There are no adequate and well-controlled studies in pregnant women. Procardia should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established. Use in pediatric population is not recommended.

Geriatric Use

Although small pharmacokinetic studies have identified an increased half-life and increased Cmax 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 response 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.

In multiple-dose U.S. 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.

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:

Incidence Approximately 10%

Cardiovascular: peripheral edema
Central Nervous System: dizziness or lightheadedness
Gastrointestinal: nausea
Systemic: headache and flushing, weakness

Incidence Approximately 5%

Cardiovascular: transient hypotension

Incidence 2% or Less

Cardiovascular: palpitation
Respiratory: nasal and chest congestion, shortness of breath
Gastrointestinal: diarrhea, constipation, cramps, flatulence
Musculoskeletal: inflammation, joint stiffness, muscle cramps
Central Nervous System: shakiness, nervousness, jitteriness, sleep disturbances, blurred vision, difficulties in balance
Other: dermatitis, pruritus, urticaria, fever, sweating, chills, sexual difficulties

Incidence Approximately 0.5%

Cardiovascular: syncope (mostly with initial dosing and/or an increase in dose), erythromelalgia

Incidence Less Than 0.5%

Hematologic: thrombocytopenia, anemia, leukopenia, purpura
Gastrointestinal: allergic hepatitis
Face and Throat: angioedema (mostly oropharyngeal edema with breathing difficulty in a few patients), gingival hyperplasia
CNS: depression, paranoid syndrome
Special Senses: transient blindness at the peak of plasma level, tinnitus
Urogenital: nocturia, polyuria
Other: arthritis with ANA (+), exfoliative dermatitis, gynecomastia
Musculoskeletal: myalgia

Several of these side effects appear to be dose related. Peripheral edema occurred in about one in 25 patients at doses less than 60 mg per day and in about one patient in eight at 120 mg per day or more. Transient hypotension, generally of mild to moderate severity and seldom requiring discontinuation of therapy, occurred in one of 50 patients at less than 60 mg per day and in one of 20 patients at 120 mg per day or more.

Very rarely, introduction of Procardia therapy was associated with an increase in anginal pain, possibly due to associated hypotension. Transient unilateral loss of vision has also occurred.

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 as well as angina pectoris (about 10% of the total patient population), 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 dermatitis caused by nifedipine. There have been rare reports of exfoliative or bullous skin adverse events (such as erythema multiforme, Stevens-Johnson Syndrome, and toxic epidermal necrolysis) and photosensitivity reactions.