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
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
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 |
ActionsActions
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.
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 |
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 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.
More Fenoldopam resources
- Fenoldopam Side Effects (in more detail)
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- Fenoldopam Drug Interactions
- Fenoldopam Support Group
- 0 Reviews for Fenoldopam - Add your own review/rating
- Fenoldopam Prescribing Information (FDA)
- Corlopam Prescribing Information (FDA)
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