Label Changes for:
Cardene (nicardipine hydrochloride) premixed injection
Changes have been made to the WARNINGS, PRECAUTIONS and ADVERSE REACTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) – January 2010
WARNINGS AND PRECAUTIONS
Excessive Pharmacodynamic Effects (reworded)
- In administering nicardipine, close monitoring of blood pressure and heart rate is required. Nicardipine may occasionally produce symptomatic hypotension or tachycardia. Avoid systemic hypotension when administering the drug to patients who have sustained an acute cerebral infarction or hemorrhage.
Use in Patients with Heart Failure (first paragraph reworded)
- Titrate slowly when using Cardene I.V. Premixed Injection, particularly in combination with a beta-blocker, in patients with heart failure or significant left ventricular dysfunction because of possible negative inotropic effects.
Use in Patients with Impaired Hepatic Function (first paragraph reworded)
- Since nicardipine is metabolized in the liver, consider lower dosages and closely monitor
responses in patients with impaired liver function or reduced hepatic blood flow.
Use in Patients with Impaired Renal Function
- When Cardene I.V. was given to mild to moderate hypertensive patients with moderate renal impairment, a significantly lower systemic clearance and higher area under the curve (AUC) was observed. These results are consistent with those seen after oral administration of nicardipine. Titrate carefully in patients with renal impairment.
Adverse Reactions Observed in Clinical Trials
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
Adverse Reactions Observed in Clinical Trials
- the Adverse Event table has been shortened
- However, titrate slowly when using Cardene I.V. Premixed Injection in combination with a beta-blocker in heart failure patients.
- Cimetidine has been shown to increase nicardipine plasma concentrations with oral nicardipine administration. Patients receiving cimetidine and Cardene I.V. Premixed Injection concomitantly should be carefully monitored. Data with other histamine-2 antagonists are not available.
USE IN SPECIFIC POPULATIONS
Pregnancy (entire section change)
- There are no adequate and well-controlled studies of nicardipine use in pregnant women. However, limited human data in pregnant women with preeclampsia or pre-term labor are available. In animal studies, no embryotoxicity occurred in rats with oral doses 8 times the maximum recommended human dose (MRHD) based on body surface area (mg/m2), but did occur in rabbits with oral doses at 24 times the maximum recommended human...
- Nicardipine is minimally excreted into human milk. Among 18 infants exposed to nicardipine through breast milk in the postpartum period, calculated daily infant dose was less than 0.3 mcg and there were no adverse events observed. Consider the possibility of infant exposure when using nicardipine in nursing mothers.
- In a study of 11 women who received oral nicardipine 4 to 14 days postpartum, 4 women received immediate-release nicardipine 40 to 80 mg daily, 6 received sustained-release nicardipine 100 to 150 mg daily, and one received intravenous nicardipine 120 mg daily.
The peak milk concentration was 7.3 mcg/L (range 1.9-18.8), and the mean milk concentration was 4.4 mcg/L (range 1.3-13.8). Infants received an average of 0.073% ofthe weight-adjusted maternal oral dose and 0.14% of the weight-adjusted maternal intravenous dose.
- In another study of seven women who received intravenous nicardipine for an average of 1.9 days in the immediate postpartum period as therapy for pre-eclampsia, 34 milk samples were obtained at unspecified times and nicardipine was undetectable (<5 mcg/L) in 82% of the samples. Four women who received 1 to 6.5 mg/hour of nicardipine had 6 milk samples with detectable nicardipine levels (range 5.1 to 18.5 mcg/L). The highest concentration of 18.5 mcg/L was found in a woman who received 5.5 mg/hour of nicardipine. The estimated maximum dose in a breastfed infant was < 0.3 mcg daily or between 0.015 to 0.004% of the therapeutic dose in a 1 kg infant.