Fenoldopam

Class: Direct Vasodilators
VA Class: AU100
Chemical Name: 6-Chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-[1H]-3-benzazepine-7,8-diol methanesulfonate
Molecular Formula: C16H16ClNO3·CH3SO3H
CAS Number: 67227-57-0
Brands: Corlopam

Introduction

Benzazepine-derivative vasodilating agent.1 10 11 12

Uses for Fenoldopam

Severe Hypertension

Used for short-term (up to 48 hours) management of severe hypertension in adults when rapid, but quickly reversible, emergency reduction of BP is clinically indicated (e.g., malignant hypertension with deteriorating end-organ function) in an inpatient setting.1 10 Transition to oral therapy with another antihypertensive agent may begin any time after BP is stable during fenoldopam infusion.1 10

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Used for short-term (up to 4 hours) management of hypertension in pediatric patients in an inpatient setting.1

Hypotensive efficacy similar to that of sodium nitroprusside in adults with severe hypertension.1 10 11 12 13 14

Unlike sodium nitroprusside, fenoldopam is not associated with thiocyanate toxicity and is not degraded by light.10 11

May have beneficial effects on renal function;10 11 13 particularly useful in patients with severe hypertension associated with end-organ renal damage or volume overload (e.g., CHF, chronic renal insufficiency).11 14

Fenoldopam Dosage and Administration

General

  • Pediatric patients: Continuously monitor heart rate and BP, usually via an intra-arterial line.1

  • Adults: Monitor BP and heart rate at frequent intervals, usually every 10–15 minutes; intra-arterial BP monitoring not required in adults.1 10

  • Avoid hypotension and rapid decreases in BP.1

  • May abruptly discontinue fenoldopam infusion1 14 or gradually taper prior to discontinuance of therapy.1 10 14

  • May administer oral antihypertensive agents during fenoldopam infusion or following discontinuance of the infusion.1

Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion only.1 Do not administer by rapid IV (bolus) injection.1

IV Administration

Administer by IV infusion using a calibrated, mechanical infusion pump to allow precise measurement of flow rate.1 In pediatric patients, use a calibrated, mechanical infusion pump appropriate for the delivery of low infusion rates.1

Dilution

Prior to administration, dilute fenoldopam injection concentrate in 0.9% sodium chloride injection or 5% dextrose injection.1

A final concentration of 60 mcg/mL generally recommended for pediatric use and 40 mcg/mL recommended for adult use.1

Solutions for pediatric patients: Add 3, 1.5, or 0.6 mL (30, 15, or 6 mg) of fenoldopam injection concentrate to 500, 250, or 100 mL, respectively, of diluent to achieve an infusion solution with a final concentration of 60 mcg/mL.1 It may be necessary to increase concentration of fenoldopam in the infusion solutions because of volume overload.1 Low flow rates (e.g., <0.5 mL/hour) may be impractical.1

Solutions for adults: Add 4, 2, or 1 mL (40, 20, or 10 mg) of fenoldopam injection concentrate to 1000, 500, or 250 mL, respectively, of diluent to achieve an infusion solution with a final concentration of 40 mcg/mL.1

Rate of Administration

Pediatric patients: Individualize rate of administration according to body weight and desired rapidity and extent of pharmacodynamic effect (see Dosage: Pediatric Patients under Dosage and Administration).1

Adults: Individualize rate of administration according to body weight and desired rapidity and extent of pharmacodynamic effect (see Dosage: Adults under Dosage and Administration.).1

Dosage

Available as fenoldopam mesylate; dosage expressed in terms of fenoldopam.1

Pediatric Patients

Severe Hypertension
IV

Usual initial dosage: 0.2 mcg/kg per minute.1 May increase dosage every 20–30 minutes by up to 0.3–0.5 mcg/kg per minute.1 Maximum effect observed at 0.8 mcg/kg per minute.1

Select initial dosage based on desired magnitude and rate of BP reduction for given clinical situation.1 Consult manufacturer’s labeling for detailed information on pharmacodynamic effects of fenoldopam dosages ranging from 0.05–3.2 mcg/kg per minute in pediatric patients.1

Adults

Severe Hypertension
IV

Usual initial dosage: 0.1–0.3 mcg/kg per minute.1 12 14 To achieve desired therapeutic effect, may titrate dosage upward or downward in increments of 0.05–0.1 mcg/kg per minute,1 14 no more frequently than every 15 minutes (and less frequently as goal BP is approached).1

Dosages <0.1 mcg/kg per minute have very modest effects and appear only marginally useful.1 Lower initial dosages (0.03–0.1 mcg/kg per minute) titrated slowly are associated with less reflex tachycardia than higher initial dosages (≥0.3 mcg/kg per minute).1 It appears that higher dosages (0.8 mcg/kg per minute) were not associated with greater response than 0.4 mcg/kg per minute.1

Select initial dosage based on desired magnitude and rate of BP reduction for given clinical situation.1 Consult manufacturer’s labeling for detailed information on pharmacodynamic effects of fenoldopam dosages ranging from 0.01–0.3 mcg/kg per minute in patients with severe hypertension.1

Prescribing Limits

Pediatric Patients

Severe Hypertension
IV

Dosages >0.8 mcg/kg per minute result in increased tachycardia without further decrease in mean arterial pressure.1 Treatment duration should not exceed 4 hours.1

Adults

Severe Hypertension
IV

Dosages up to 1.6 mcg/kg per minute studied.1 Treatment duration should not exceed 48 hours.1

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.1

Renal Impairment

No specific dosage recommendations at this time.1

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Cautions for Fenoldopam

Contraindications

  • Manufacturer states that there are no known contraindications to use of fenoldopam.1

Warnings/Precautions

Sensitivity Reactions

Sulfite Sensitivity

Commercially available formulations contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.1 2 3 4 5 6 7 8 9

General Precautions

Cardiovascular Effects

Dose-related tachycardia reported, especially in patients receiving infusion rates >0.1 mcg/kg per minute.1 In adults, tachycardia diminishes over time but remains substantial at higher dosages.1 In pediatric patients receiving dosages >0.8 mcg/kg per minute, tachycardia persists for at least 4 hours.1

Theoretical risk of ischemic cardiac events or worsened heart failure secondary to tachycardia associated with fenoldopam.1

Symptomatic hypotension reported.1 Avoid systemic hypotension, particularly in patients with acute cerebral infarction or hemorrhage.1

Hypokalemia

Decreases in serum potassium (occasionally to concentration <3 mEq/L) reported after <6 hours of fenoldopam infusion.1 Monitor serum electrolytes frequently (e.g., every 6 hours).1 In case of hypokalemia, treat with oral or IV potassium supplementation as needed.1

Intraocular Pressure (IOP)

Dose-dependent, reversible increases in IOP reported.1 10 14 Use with caution in patients with glaucoma or intraocular hypertension.1 14

Intracranial Pressure

Effect of fenoldopam in patients with increased intracranial pressure not studied to date.1

Adequate Patient Monitoring

Adults: Monitor BP and serum electrolytes frequently.1 Also monitor heart rate.1

Pediatric patients: Continuously monitor heart rate and BP.1 15

Specific Populations

Pregnancy

Category B.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Use caution.1

Pediatric Use

In pediatric patients, administer fenoldopam only in those with an indwelling intra-arterial line.1

Antihypertensive effects of fenoldopam evaluated in pediatric patients (age <1 month [≥2 kg or full term] to 12 years) requiring BP reduction.1 Continuously monitor heart rate and BP in pediatric patients, via an indwelling intra-arterial line.1

Long-term effects of fenoldopam on growth and development in pediatric patients have not been studied.1

Insufficient experience in patients 12–16 years of age to determine whether children in this age group respond differently than younger patients or adults.1 Consider patient’s clinical condition and concomitant drug therapy when selecting dosage in pediatric patients 12–16 years of age.1

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution.1 (See Geriatric Patients under Dosage and Administration.)

Common Adverse Effects

Adults: Headache,1 10 11 12 14 flushing,1 10 11 12 14 nausea,1 12 14 hypotension,1 12 hypokalemia.12

Pediatric patients: Hypotension,1 tachycardia.1

Interactions for Fenoldopam

Not metabolized by CYP isoenzymes.1

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Pharmacokinetic interaction unlikely1 14

α-Adrenergic blocking agents

Pharmacokinetic interaction unlikely1

β-Adrenergic blocking agents

May cause unexpected hypotension secondary to β-blocker inhibition of sympathetic reflex response to fenoldopam1

Avoid concomitant use; if used concomitantly, exercise caution1

Calcium-channel blocking agents

Pharmacokinetic interaction unlikely1

Cardiac glycosides

Pharmacokinetic interaction unlikely1 11 15

Diuretics (thiazide-like, loop)

Pharmacokinetic interaction unlikely1

Nitroglycerin (sublingual)

Pharmacokinetic interaction unlikely1 15

Fenoldopam Pharmacokinetics

Absorption

Onset

Adults: Rapid onset of response.1 11 12 Most of the antihypertensive effect attained in 15 minutes.1 11 15

Pediatric patients: Effect on BP and heart rate evident within 5 minutes after starting infusion.1 Effects increased with time for 15–25 minutes; an effect was still observed at an average of 4 hours after initiation of the infusion.1

Duration

Adults: Substantial effect persisted through 48 hours of continuous infusion.1 Following discontinuance of fenoldopam infusion, BP gradually returned to pretreatment values with no evidence of rebound hypertension.1 12 14

Pediatric patients: BP and heart rate approached baseline values during the 30 minutes following discontinuance of fenoldopam infusion.1

Distribution

Extent

Distributed into milk in rats; not known whether distributed into human milk.1

Only minimal amounts (≤0.005%) cross the blood-brain barrier.1 10

Plasma Protein Binding

Approximately 85–90%.10 14

Elimination

Metabolism

Metabolized principally by conjugation (methylation, glucuronidation, sulfation)1 11 14 to inactive metabolites.1 Not metabolized by cytochrome P-450 enzymes.1

Elimination Route

Excreted in urine (90%) mainly as inactive metabolites and in feces (10%).1 About 4% of the dose is excreted unchanged.1

Half-life

Adults: About 5–10 minutes.1 10 11 14

Pediatric patients (1 month to 12 years of age): About 3–5 minutes.1

Special Populations

Clearance of fenoldopam is not altered in patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis (CAPD) or in patients with severe hepatic failure.1 Effects of hemodialysis on pharmacokinetics of fenoldopam not evaluated.1

Stability

Storage

Parenteral

Injection

2–30°C.1

Ampuls of fenoldopam injection concentrate are for single use only.1

Diluted solutions are stable under normal ambient light and temperature conditions for at least 24 hours.1 Use diluted solutions within 24 hours; discard thereafter.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in water

Sodium chloride 0.9%

Drug CompatibilityHID
Y-Site Injection Compatibility

Compatible

Alfentanil HCl

Amikacin sulfate

Aminocaproic acid

Amiodarone HCl

Ampicillin sodium-sulbactam sodium

Argatroban

Atracurium besylate

Atropine sulfate

Aztreonam

Bretylium tosylate

Butorphanol tartrate

Calcium gluconate

Cefazolin sodium

Cefepime HCl

Cefotaxime sodium

Cefotetan disodium

Ceftazidime

Ceftizoxime sodium

Ceftriaxone sodium

Cefuroxime sodium

Chlorpromazine HCl

Cimetidine HCl

Ciprofloxacin

Cisatracurium besylate

Clindamycin phosphate

Co-trimoxazole

Dexmedetomidine HCl

Digoxin

Diltiazem HCl

Diphenhydramine HCl

Dobutamine HCl

Dolasetron mesylate

Dopamine HCl

Doxycycline hyclate

Droperidol

Enalaprilat

Ephedrine sulfate

Epinephrine HCl

Erythromycin lactobionate

Esmolol HCl

Famotidine

Fentanyl citrate

Fluconazole

Gatifloxacin

Gentamicin sulfate

Granisetron HCl

Haloperidol lactate

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Hydrocortisone sodium succinate

Hydromorphone HCl

Hydroxyzine HCl

Inamrinone lactate

Isoproterenol HCl

Labetalol HCl

Levofloxacin

Lidocaine HCl

Linezolid

Lorazepam

Magnesium sulfate

Mannitol

Meperidine HCl

Metoclopramide HCl

Metronidazole

Midazolam HCl

Milrinone lactate

Mivacurium chloride

Morphine sulfate

Nalbuphine HCl

Naloxone HCl

Nicardipine HCl

Nitroglycerin

Norepinephrine bitartrate

Ondansetron HCl

Pancuronium bromide

Phenylephrine HCl

Piperacillin sodium-tazobactam sodium

Potassium chloride

Procainamide HCl

Promethazine HCl

Propofol

Propranolol HCl

Quinupristin-dalfopristin

Ranitidine HCl

Remifentanil HCl

Rocuronium bromide

Sufentanil citrate

Theophylline

Ticarcillin disodium-clavulanate potassium

Tobramycin sulfate

Vancomycin

Vecuronium bromide

Verapamil HCl

Incompatible

Aminophylline

Amphotericin B

Ampicillin sodium

Bumetanide

Cefoxitin sodium

Dexamethasone sodium phosphate

Diazepam

Fosphenytoin sodium

Furosemide

Ketorolac tromethamine

Methylprednisolone sodium succinate

Pentobarbital sodium

Phenytoin sodium

Prochlorperazine edisylate

Sodium bicarbonate

Thiopental sodium

Actions

  • Agonist for D1-like dopamine receptors; binds with moderate affinity to α2-adrenoreceptors.1 10 11 12 13 14 Not a selective α-adrenoreceptor antagonist at therapeutic concentrations.11

  • Rapid-acting vasodilator.1 10 12 14

  • In animals, has vasodilating effects in coronary, renal, mesenteric, and peripheral arteries; however, all vascular beds do not respond uniformly to the drug.1

  • Vasodilating effects have been demonstrated in renal efferent and afferent arterioles.1

  • In patients with severe hypertension, produces dose-related, rapid-onset decreases in SBP and DBP and dose-related increases in heart rate.1 11

  • May increase plasma norepinephrine concentration.1

    May have beneficial effects on renal function; increases in urinary output, sodium excretion, and Clcr observed in patients with severe hypertension, including those with renal impairment.10 11 13 14

Advice to Patients

  • 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.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Fenoldopam Mesylate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection concentrate, for IV infusion only

10 mg (of fenoldopam)/mL

Corlopam (with propylene glycol and sodium metabisulfite)

Hospira

Fenoldopam Mesylate Injection (with propylene glycol and sodium metabisulfite)

Ben Venue Laboratories

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Hospira. Corlopam (fenoldopam mesylate injection) prescribing information. Lake Forest, IL; 2005 Mar.

2. Food and Drug Administration. Sulfites in foods and drugs. FDA Drug Bull. 1983; 13:12. [PubMed 6604672]

3. Sogn D. The ubiquitous sulfites. JAMA. 1984; 251:2986 7. Editorial. [IDIS 185969] [PubMed 6716628]

4. Koepke JW, Christopher KL, Chai H et al. Dose dependent bronchospasm from sulfites in isoetharine. JAMA. 1984; 251:2982 3. [IDIS 185966] [PubMed 6716626]

5. Twarog FJ, Leung DYM. Anaphylaxis to a component of isoetharine (sodium bisulfite). JAMA. 1982; 248:2030 1. [IDIS 158261] [PubMed 7120631]

6. Baker GJ, Collett P, Allen DH. Bronchospasm induced by metabisulphite containing foods and drugs. Med J Aust. 1981; 2:614 7. [IDIS 146240] [PubMed 7334982]

7. Koepke JW, Selner JC, Dunhill AL. Presence of sulfur dioxide in commonly used bronchodilator solutions. J Allergy Clin Immunol. 1983; 72:504 8. [IDIS 178793] [PubMed 6630799]

8. Food and Drug Administration. Sulfiting agents; labeling in drugs for human use: warning statement. [Docket No. 84N 0113] Fed Regist. 1985; 50:47558 63.

9. Food and Drug Administration Center for Food Safety and Applied Nutrition. The reexamination of the GRAS status of sulfiting agents, January 1985. (Doc. No. 223-83-2020.) Bethesda, MD: FASEB Life Sciences Research Office.

10. Murphy MB, Murray C, Shorten GD. Fenoldopam—a selective peripheral dopamine-receptor agonist for the treatment of severe hypertension. N Engl J Med. 2001; 345:1548-57. [PubMed 11794223]

11. Post JB IV, Frishman WH. Fenoldopam: a new dopamine agonist for the treatment of hypertensive urgencies and emergencies. J Clin Pharmacol. 1998; 38:2-13. [PubMed 9597553]

12. Panacek EA, Bednarczyk EM, Dunbar LM et al. Randomized, prospective trial of fenoldopam vs sodium nitroprusside in the treatment of acute severe hypertension. Acad Emerg Med. 1995; 2:959-65. [PubMed 8536121]

13. Shusterman NH, Elliott WJ. Fenoldopam, but not nitroprusside, improves renal function in severely hypertensive patients with impaired renal function. Am J Med. 1993; 95:161-8. [PubMed 8102835]

14. Brogden RN, Markham A. Fenoldopam: a review of its pharmacodynamic and pharmacokinetic properties and intravenous clinical potential in the management of hypertensive urgencies and emergencies. Drugs. 1997; 54:634-50. [PubMed 9339965]

15. Hospira, Lake Forest, IL: Personal communication.

16. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 691-8.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 691-8.

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