Side Effects of Cardene (nicardipine)

Cardene (nicardipine) is a calcium channel blocker (CCB) used to treat high blood pressure (hypertension) and angina (heart pain). 

In order to pump blood, the heart needs oxygen. The harder the heart works, the more oxygen it requires. 

Angina (heart pain) occurs when the supply of oxygen to the heart is inadequate for the amount of work that the heart must do. By dilating the arteries, calcium channel blockers such as 

Cardene reduces the pressure in the arteries. This makes it easier for the heart to pump blood, and, as a result, the heart needs less oxygen. By reducing the heart's need for oxygen, calcium channel blockers relieve or prevent angina. 

Calcium channel blockers also are used to treat high blood pressure because of their blood pressure-lowering effects. Calcium channel blockers decrease the excitability of heart muscle and are used for treating certain types of abnormally rapid heart rhythms.

Common side effects of Cardene include

• swelling of the feet (edema),
• dizziness,
• headaches,
• flushing,
• palpitations, and
• nausea.

Serious side effects of Cardene include

• fainting,
• overgrowth of the gums,
• rash,
• increased heart rate due to a drop in blood pressure,
• increased frequency and duration of angina, and
• excessively low blood pressure in rare instances, especially during initiation of treatment or following adjustments of dosage.

Drug interactions of Cardene include rifampin, phenobarbital, phenytoin, oxcarbazepine, and carbamazepine, because they may reduce blood levels of Cardene by increasing its metabolism in the liver. 

• Itraconazole, ketoconazole, or clarithromycin may increase blood levels of Cardene by reducing its breakdown in the liver and lead to toxicity from Cardene. 
• Co-administration of Cardene and cyclosporine results in increased cyclosporine blood levels. 

There are no adequate studies of Cardene in pregnant women; Cardene has been used to treat the high blood pressure of preeclampsia during the third trimester of pregnancy. 

Animal studies show Cardene is secreted in breast milk. Cardene should be avoided by breastfeeding mothers.

Side effects include:

• swelling of the feet (edema),
• dizziness,
• headaches,
• flushing,
• palpitations, and
• nausea.

Fainting, over growth of the gums, and rash also may occur. It may increase heart rate due to a drop in blood pressure. Nicardipine sometimes causes an increase in the frequency and duration of angina.

The reason for this side effect is not clearly understood. Excessively low blood pressure can occur in rare instances, especially during initiation of treatment or following adjustments of dosage.

In multiple-dose US and foreign controlled studies, 667 patients received Cardene SR. In these studies adverse events were elicited by non-directed and in some cases directed questioning; adverse events were generally not serious and about 9% of patients withdrew prematurely from the studies because of them.

Hypertension

The incidence rates of adverse events in hypertensive patients were derived from placebo-controlled clinical trials. Following are the rates of adverse events for Cardene SR (n=322) and placebo (n=140), respectively, that occurred in 0.6% of patients or more on Cardene SR.

These represent events considered probably drug related by the investigator. Where the frequency of adverse events for Cardene SR and placebo is similar, causal relationship is uncertain. The only dose-related effect was pedal edema.

Percentage of Patients With Probably Drug Related Adverse Events in Placebo-Controlled Studies

Incidence (%) of Discontinuations Due to Any Adverse Event in Placebo-Controlled Studies

Uncontrolled experience in over 300 patients with hypertension treated for up to 27.5 months with Cardene SR has shown no unexpected adverse events or increase in incidence of adverse events compared to the controlled clinical trials.

Rare Events

The following rare adverse events have been reported in clinical trials or the literature:

Body as a Whole: infection, allergic reaction

Cardiovascular: hypotension, atypical chest pain, peripheral vascular disorder, ventricular extrasystoles, ventricular tachycardia, angina pectoris

Digestive: sore throat, abnormal liver chemistries

Musculoskeletal: arthralgia

Nervous: hot flashes, vertigo, hyperkinesia, impotence, depression, confusion, anxiety

Respiratory: rhinitis, sinusitis

Special Senses: tinnitus, abnormal vision, blurred vision

Angina

Data are available from only 91 patients with chronic stable angina pectoris who received Cardene SR 30 to 60 mg administered twice daily in open-label clinical trials. Fifty-eight of these patients were treated for at least 30 days.

The four most frequently reported adverse events thought by the investigators to be probably related to the use of Cardene SR were

• vasodilatation (5.5%),
• pedal edema (4.4%),
• asthenia (4.4%), and
• dizziness (3.3%).

Beta-Blockers:

In controlled clinical studies, adrenergic beta-receptor blockers have been frequently administered concomitantly with Cardene. The combination is well tolerated.

Cimetidine:

Cimetidine increases Cardene plasma levels. Patients receiving the two drugs concomitantly should be carefully monitored.

Digoxin:

Some calcium blockers may increase the concentration of digitalis preparations in the blood. Cardene usually does not alter the plasma levels of digoxin; however, serum digoxin levels should be evaluated after concomitant therapy with Cardene is initiated.

Fentanyl Anesthesia:

Severe hypotension has been reported during fentanyl anesthesia with concomitant use of a beta-blocker and a calcium channel blocker. Even though such interactions were not seen during clinical studies with Cardene, an increased volume of circulating fluids might be required if such an interaction were to occur.

Cyclosporine:

Concomitant administration of nicardipine and cyclosporine results in elevated plasma cyclosporine levels. Plasma concentrations of cyclosporine should therefore be closely monitored, and its dosage reduced accordingly, in patients treated with nicardipine.

When therapeutic concentrations of furosemide, propranolol, dipyridamole, warfarin, quinidine or naproxen were added to human plasma (in vitro), the plasma protein binding of Cardene was not altered.