Fenoldopam

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• If you are allergic to sulfites, talk with your doctor. Some products have sulfites.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using fenoldopam while you are pregnant.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

Intraocular Pressure

In a clinical study of 12 patients with open-angle glaucoma or ocular hypertension (mean baseline intraocular pressure was 29.2 mmHg with a range of 22 to 33 mmHg), infusion of Fenoldopam at escalating doses ranging from 0.05 to 0.5 mcg/kg/min over a 3.5 hour period caused a dose-dependent increase in intraocular pressure (IOP). At the peak effect, the intraocular pressure was raised by a mean of 6.5 mmHg (range -2 to +8.5 mmHg, corrected for placebo effect). Upon discontinuation of the Fenoldopam infusion, the IOP returned to baseline values within 2 hours. Fenoldopam Mesylate Injection, USP administration to patients with glaucoma or intraocular hypertension should be undertaken with caution.

Tachycardia

Fenoldopam causes a dose-related tachycardia (Table 2 and Table 3), particularly with infusion rates above 0.1 mcg/kg/min.

Tachycardia in adults diminishes over time but remains substantial at higher doses. Tachycardia in pediatric patients at doses ≥ 0.8 mcg/kg/min persists at least for 4 hours.

Hypotension

Fenoldopam may occasionally produce symptomatic hypotension and close monitoring of blood pressure during administration is essential. (See ADVERSE REACTIONS). It is particularly important to avoid systemic hypotension when administering the drug to patients who have sustained an acute cerebral infarction or hemorrhage.

In pediatric patients, Fenoldopam was only administered to patients with an indwelling intra-arterial line.

Hypokalemia

Decreases in serum potassium occasionally to values below 3 mEq/L were observed after less than 6 hours of Fenoldopam infusion. It is not clear if the hypokalemia reflects a pressure natriuresis with enhanced potassium-sodium exchange or a direct drug effect. During clinical trials, electrolytes were monitored at intervals of 6 hours. Hypokalemia was treated with either oral or intravenous potassium supplementation. Patient management should include appropriate attention to serum electrolytes.

Intracranial Pressure

The effect of Fenoldopam in the presence of increased intracranial pressure has not been studied.

Drug Interactions with Beta-Blockers

Concomitant use of Fenoldopam with beta-blockers should be avoided. If the drugs are used together, caution should be exercised because unexpected hypotension could result from beta-blocker inhibition of the sympathetic reflex response to Fenoldopam.

Drug Interactions: General

Although there have been no formal interaction studies, intravenous Fenoldopam has been administered safely with drugs such as digitalis and sublingual nitroglycerin. There is limited experience with concomitant antihypertensive agents such as alpha-blockers, calcium channel-blockers, ACE inhibitors, and diuretics (both thiazide-like and loop).

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 24-month study, mice treated orally with Fenoldopam at 12.5, 25, or 50 mg/kg/day, reduced to 25 mg/kg/day on day 209 of study, showed no increase above controls in the incidence of neoplasms. Female mice in the highest dose group had an increased incidence and degree of severity of a fibro-osseous lesion of the sternum compared with control or low-dose animals. Compared to controls, female mice in the middle- and upper-dose groups had a higher incidence and degree of severity of chronic nephritis. These pathologic lesions were not seen in male mice treated with Fenoldopam.

In a 24-month study, rats treated orally with Fenoldopam at 5, 10 or 20 mg/kg/day, with the mid- and high-dose groups increased to 15 or 25 mg/kg/day, respectively, on day 372 of the study, showed no increase above controls in the incidence or type of neoplasms. Compared with the controls, rats in the mid- and high-dose groups had a higher incidence of hyperplasia of collecting duct epithelium at the tip of the renal papilla.

Fenoldopam did not induce bacterial gene mutation in the Ames test or mammalian gene mutation in the Chinese hamster ovary (CHO) cell assay. In the in vitro chromosomal aberration assay with CHO cells, Fenoldopam was associated with statistically significant and dose-dependent increases in chromosomal aberrations, and in the proportion of aberrant metaphases. However, no chromosomal damage was seen in the in vivo mice micronucleus or bone marrow assays.

Oral fertility and general reproduction performance studies in male and female rats at 12.5, 37.5 or 75 mg/kg/day revealed no impairment of fertility or reproduction performance due to Fenoldopam.

Pregnancy

Oral reproduction studies have been performed in rats and rabbits at doses of 12.5 to 200 mg/kg/day and 6.25 to 25 mg/kg/day, respectively. Studies have revealed maternal toxicity at the highest doses tested but no evidence of impaired fertility or harm to the fetus due to Fenoldopam. However, there are no adequate and well-controlled studies in pregnant women. Since animal reproduction studies are not always predictive of human response, Fenoldopam should be used in pregnancy only if clearly needed.

Nursing Mothers

Fenoldopam is excreted in milk in rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Fenoldopam is administered to a nursing woman.

Pediatric Use

Anti-hypertensive effects of Fenoldopam have been studied in pediatric patients age <1 month (at least 2 kg or full term) to 12 years old requiring blood pressure reduction (see Pharmacodynamics and Clinical Studies: Pediatric Patients).

Clinical studies of Fenoldopam did not include subjects ages 12 to 16 years of age to determine if they respond differently from younger subjects or adults. The pharmacokinetics of Fenoldopam are independent of age when corrected for body weight. Dose selection for patients 12 to 16 years of age should consider the patient's clinical condition and concomitant drug therapy.

Geriatric Use

Clinical studies of Fenoldopam 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 responses 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.

Adult Patients

The optimal magnitude and rate of blood pressure reduction in acutely hypertensive patients have not been rigorously determined, but, in general, both delay and too rapid decreases appear undesirable in sick adult patients. An initial Fenoldopam Mesylate Injection, USP dose may be chosen from Table 2 and 3 in the Clinical Pharmacology Section that produces the desired magnitude and rate of blood pressure reduction in a given clinical situation. Doses below 0.1 mcg/kg/min have very modest effects and appear only marginally useful in this population. In general, as the initial dose increases, there is a greater and more rapid blood pressure reduction. However, lower initial doses (0.03 to 0.1 mcg/kg/min) titrated slowly have been associated with less reflex tachycardia than have higher initial doses (≥0.3 mcg/kg/min). In clinical trials, doses from 0.01 to 1.6 mcg/kg/min have been studied. Most of the effect of a given infusion rate is attained in 15 minutes.

Fenoldopam Mesylate Injection, USP should be administered by continuous intravenous infusion. A bolus dose should not be used. Hypotension and rapid decreases of blood pressure should be avoided. The initial dose should be titrated upward or downward, no more frequently than every 15 minutes (and less frequently as goal pressure is approached) to achieve the desired therapeutic effect. The recommended increments for titration are 0.05 to 0.1 mcg/kg/min.

Use of a calibrated, mechanical infusion pump is recommended for proper control of infusion rate during Fenoldopam Mesylate Injection, USP infusion. In clinical trials, Fenoldopam treatment was safely performed without the need for intra-arterial blood pressure monitoring; blood pressure and heart rate were monitored at frequent intervals, typically every 15 minutes. Frequent blood pressure monitoring is recommended.

The Fenoldopam Mesylate Injection, USP infusion can be abruptly discontinued or gradually tapered prior to discontinuation. Oral antihypertensive agents can be added during Fenoldopam Mesylate Injection, USP infusion or following its discontinuation. Patients in controlled clinical trials have received intravenous Fenoldopam for as long as 48 hours.

WARNING

CONTENTS OF AMPULES MUST BE DILUTED BEFORE INFUSION. EACH AMPULE IS FOR SINGLE USE ONLY.

Dilution

The Fenoldopam Mesylate Injection, USP ampule concentrate must be diluted in 0.9% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP, using the following dilution schedule:

The drug dose rate must be individualized according to body weight and according to the desired rapidity and extent of pharmacodynamic effect. Table 5 provides the calculated infusion volume in mL/hour for a range of drug doses and body weights. The infusion should be administered using a calibrated mechanical infusion pump that can accurately and reliably deliver the desired infusion rate.

The diluted solution is stable under normal ambient light and temperature conditions for at least 24 hours. Diluted solution that is not used within 24 hours of preparation should be discarded. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If particulate matter or cloudiness is observed, the drug should be discarded.

Fenoldopam should be administered intravenously to pediatric patients by a continuous infusion pump appropriate for the delivery of low infusion rates. Monitoring of blood pressure should be continuous, usually by way of an intra-arterial line. Heart rate should also be continuously monitored. In the clinical trial, the usual starting dose was 0.2 mcg/kg/min with an effect on MAP evident within 5 minutes. At a constant infusion rate the effect was maximal after 20 to 25 minutes. Increased dosages of up to 0.3 to 0.5 mcg/kg/min every 20 to 30 minutes were generally well tolerated. Tachycardia without further decrease in MAP occurred at dosages greater than 0.8 mcg/kg/min. Upon discontinuation of the Fenoldopam infusion after an average of 4 hours of therapy, blood pressure and heart rate returned to near baseline within 30 minutes.

NDC 0781-3005-71

Fenoldopam

Mesylate

Injection, USP

10 mg/mL

Rx only

DILUTE PRIOR TO IV INFUSION

Sterile

1 mL Ampule

SANDOZ

(fe NOL doe pam)

Refer to adult dosing.

Store undiluted product at 2°C to 30°C (35°F to 86°F). Diluted solutions in NS or D5W that have been prepared but not administered should be discarded after 4 hours at room temperature or 24 hours refrigerated.

Fetal harm was not observed in animal studies; however, safety and efficacy have not been established for use during pregnancy. Use during pregnancy only if clearly needed.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, flushing, nausea, or injection site pain or irritation. Have patient report immediately to prescriber signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), tachycardia, severe dizziness, or passing out (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.