Side Effects of Procardia (nifedipine)

Procardia (nifedipine) is a calcium channel blocker (CCB) used to treat and prevent angina (heart pain) resulting from either an increased workload on the heart (as with exercise) or spasm of the coronary arteries.

Procardia is also used to treat high blood pressure, to treat abnormally fast heart rhythms such as atrial fibrillation, and to prevent episodes of abnormal rapid heart rhythm originating from the atria of the heart.

It also is used to dilate blood vessels that go into spasm such as those causing Raynaud's phenomenon, a painful condition of the hands caused by spasm of the arteries supplying blood to the hands. 

Common side effects of Procardia include

• headache,
• dizziness,
• flushing, and
• swelling (edema) of the lower extremities.

Less common side effects of Procardia include nausea and constipation.

Uncommon side effects of Procardia include

• muscle cramps,
• wheezing,
• overgrowth of gums,
• erectile dysfunction, and
• excessive reduction in blood pressure.

Drug interactions of Procardia include beta blockers, which may rarely cause congestive heart failure or excessive lowering of blood pressure (hypotension).

• Procardia decreases the elimination of digoxin by the kidneys which can increase digoxin blood levels in the blood and give rise to digoxin toxicity.
• Procardia interferes with the breakdown of tacrolimus by the liver, which in turn causes elevated blood levels of tacrolimus and may increase the risk of toxicity from tacrolimus.
• Procardia reduces the blood levels of quinidine which may reduce the effectiveness of quinidine.
• Conversely, blood levels of Procardia are increased by quinidine and may lead to side effects from Procardia.
• Cimetidine interferes with breakdown by the liver of Procardia and increases Procardia blood levels.
• Procardia should not be taken with grapefruit juice since grapefruit juice inhibits the breakdown of Procardia by the liver and increases the levels of Procardia in the blood.

There are no adequate studies of Procardia in pregnant women, and in general, it is avoided during pregnancy. Procardia is excreted in human breast milk. Generally, Procardia is avoided in females who are breastfeeding.

Side effects of nifedipine are generally mild, and reversible. Most side effects are expected consequences of the dilation of the arteries. The most common side effects include:

• Headache
• Dizziness
• Flushing
• Edema (swelling) of the lower extremities

Less common side effects include:

• Nausea
• Constipation

Uncommon side effects include:

• Muscle cramps
• Wheezing
• Over growth of gums
• Erectile dysfunction
• Excessive reduction in blood pressure

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.

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 betaadrenergic 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 were not different from that of the entire group of Procardia (nifedipine) treated patients.

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. Acute generalized exanthematous pustulosis also has been reported.

Beta-adrenergic Blocking Agents

Experience in over 1400 patients in a noncomparative 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.

Long-acting Nitrates

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

Digitalis

Since there have been isolated reports of patients with elevated digoxin levels, and since 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.

Quinidine

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

Coumarin Anticoagulants

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.

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.

Nifedipine is metabolized by CYP3A4. Co-administration of nifedipine with phenytoin, an inducer of CYP3A4, lowers the systemic exposure to nifedipine by approximately 70%. Avoid co-administration of nifedipine with phenytoin or any known CYP3A4 inducer or consider an alternative antihypertensive therapy.

CYP3A inhibitors such as fluconazole, itraconazole, clarithromycin, erythromycin, nefazodone, fluoxetine, saquinavir, indinavir, and nelfinavir may result in increased exposure to nifedipine when coadministered.

Careful monitoring and dose adjustment may be necessary; consider initiating nifedipine at the lowest dose available if given concomitantly with these medications.

Other Interactions

Grapefruit Juice

Co-administration of nifedipine with grapefruit juice resulted in approximately a doubling in nifedipine AUC and Cmax with no change in half-life. The increased plasma concentrations most likely result from inhibition of CYP 3A4 related first-pass metabolism.

Avoid ingestion of grapefruit and grapefruit juice while taking nifedipine.