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Fenoldopam
Fenoldopam
Fenoldopam
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Fenoldopam
Clinical data
Trade namesCorlopam
AHFS/Drugs.comMonograph
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismHepatic (CYP not involved)
Elimination half-life5 minutes
ExcretionRenal (90%) and fecal (10%)
Identifiers
  • (RS)-6-chloro-1-(4-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC16H16ClNO3
Molar mass305.76 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
  • Clc1c3c(cc(O)c1O)C(c2ccc(O)cc2)CNCC3
  • InChI=1S/C16H16ClNO3/c17-15-11-5-6-18-8-13(9-1-3-10(19)4-2-9)12(11)7-14(20)16(15)21/h1-4,7,13,18-21H,5-6,8H2 checkY
  • Key:TVURRHSHRRELCG-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Fenoldopam, sold under the brand name Corlopam, is a drug and synthetic benzazepine derivative which acts as a selective D1 receptor partial agonist.[1] Fenoldopam is used as an antihypertensive agent.[2] It was approved by the US Food and Drug Administration (FDA) in September 1997.[3]

Medical uses

[edit]

Fenoldopam is used as an antihypertensive agent postoperatively, and also intravenously to treat a hypertensive crisis.[4] Since fenoldopam is an intravenous agent with minimal adrenergic effects that improves renal perfusion, in theory it could be beneficial in hypertensive patients with concomitant chronic kidney disease.[5] It can cause reflex tachycardia, but it is dependent on the infusion of the drug.

Contraindications

[edit]

Fenoldopam mesylate contains sodium metabisulfite, a sulfite that may rarely cause allergic-type reactions including anaphylactic symptoms and asthma in susceptible people. Fenoldopam mesylate administration should be undertaken with caution to patients with glaucoma or raised intraocular pressure as fenoldopam raises intraocular pressure.[6] Concomitant use of fenoldopam with a beta blocker should be avoided if possible, as unexpected hypotension can result from beta-blocker inhibition of sympathetic-mediated reflex tachycardia in response to fenoldopam.[6]

Adverse effects

[edit]

Adverse effects include headache, flushing, nausea, hypotension, reflex tachycardia, and increased intraocular pressure.[4][6]

Pharmacology

[edit]

Fenoldopam causes arterial/arteriolar vasodilation leading to a decrease in blood pressure by activating peripheral D1 receptors.[7] It decreases afterload and also promotes sodium excretion via specific dopamine receptors along the nephron. The renal effect of fenoldopam and dopamine may involve physiological antagonism of the renin-angiotensin system in the kidney.[8] In contrast to dopamine, fenoldopam is a selective D1 receptor agonist with no effect on beta adrenoceptors, although there is evidence that it may have some alpha-1[9] and alpha-2 adrenoceptor antagonist activity.[7] D1 receptor stimulation activates adenylyl cyclase and raises intracellular cyclic AMP, resulting in vasodilation of most arterial beds, including renal, mesenteric, and coronary arteries.[10] to cause a reduction in systemic vascular resistance. Fenoldopam has a rapid onset of action (4 minutes) and short duration of action (< 10 minutes) and a linear dose–response relationship at usual clinical doses.[11]

See also

[edit]

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Fenoldopam

View on Grokipedia
from Grokipedia
Fenoldopam is a synthetic benzazepine that functions as a selective D1-like receptor , primarily administered intravenously for the short-term management of severe in hospitalized adults and pediatric patients. It acts as a rapid-onset vasodilator by binding to peripheral in vascular and the renal vasculature, leading to decreased systemic , increased renal blood flow, , and with minimal effects on adrenergic receptors. Approved by the FDA in 1997 under the brand name Corlopam, it is indicated for in-hospital reduction lasting up to 48 hours in adults, particularly in cases of malignant with end-organ , and up to 4 hours in children. Mechanism and Pharmacology
Fenoldopam exerts its antihypertensive effects through dose-dependent activation of postsynaptic D1 receptors, promoting in renal, coronary, mesenteric, and peripheral arteries while increasing and . Its include an within 5 minutes, a short of approximately 5 minutes, hepatic , and primarily renal excretion, allowing for precise titration via continuous IV at doses ranging from 0.01 to 1.6 mcg/kg/min in adults. Unlike non-selective agonists, it spares D2 receptors and does not significantly alter function or cause at therapeutic doses. Clinical Use and Considerations
Clinically, fenoldopam has been valued for its renal-protective properties, improving glomerular filtration and urine output in patients with and compromised function, though studies show no long-term impact on mortality or need for . Common adverse effects include , flushing, , , , and , with precautions needed for patients sensitive to sulfites or in the formulation. However, manufacturing of fenoldopam was discontinued in 2023, rendering it unavailable in the United States as of 2025.

Medical uses

Indications

Although fenoldopam was FDA-approved for the following indications, its manufacturing was discontinued in 2023 by the sole manufacturer (/), and no products are currently available as of 2025. Fenoldopam is indicated for the short-term (up to 48 hours) intravenous management of severe in hospitalized adults, particularly in cases of malignant hypertension accompanied by deteriorating end-organ function, where rapid and reversible reduction is required. This includes hypertensive emergencies and urgencies necessitating immediate intervention to prevent further organ damage, with transition to oral antihypertensive recommended once stabilizes. The U.S. (FDA) approved fenoldopam for this primary indication in 1997, based on pivotal clinical trials demonstrating its ability to achieve rapid lowering—typically within 15 minutes—without causing significant end-organ damage, as evidenced in studies involving patients with mild to moderate and hypertensive emergencies. In pediatric patients, fenoldopam is approved for short-term (up to 4 hours) in-hospital reduction in those aged from neonates (≥2 kg or full-term, <1 month) to 12 years with severe . Clinical evidence from dose-ranging studies in 77 pediatric patients supports its efficacy and safety in this population, showing effective control comparable to adults but with a higher required dose range. Secondary applications include the treatment of in perioperative settings, such as after , where fenoldopam has demonstrated benefits in reducing the incidence of (AKI) through enhanced renal blood flow. A of randomized trials indicated that perioperative fenoldopam significantly lowered postoperative AKI rates in high-risk surgical patients, without impacting mortality or hospital stay. Additionally, it offers potential renoprotective effects in patients with (CKD) by improving renal plasma flow, as shown in studies of high-risk individuals undergoing procedures like , where it preserved glomerular filtration rates better than alternatives. Compared to nitroprusside, fenoldopam is often preferred in patients with renal impairment due to its selective peripheral and renal vasodilatory effects, which enhance renal function rather than potentially worsening it through cyanide accumulation. This advantage stems from fenoldopam's dopamine-1 receptor agonism, promoting vasodilation specifically in renal vasculature to support blood pressure reduction while protecting kidney perfusion.

Administration and dosage

Although detailed below, fenoldopam is no longer available for administration following its discontinuation in 2023. Fenoldopam is administered solely by continuous intravenous and is not available in oral or subcutaneous forms. The drug is supplied as a sterile injection concentrate (10 mg/mL) in single-use ampules or vials, which must be diluted prior to administration to a concentration of 40 mcg/mL or higher using compatible diluents such as 5% dextrose injection or 0.9% injection. Diluted solutions remain stable for up to 24 hours when refrigerated or 4 hours at , after which any unused portions should be discarded to prevent potential degradation or . The should be initiated using an for precise control, and compatibility with common intravenous fluids allows flexibility in clinical settings. For adult patients, initial dosing typically starts at 0.01 to 0.3 mcg/kg/min, with subsequent increases of 0.05 to 0.1 mcg/kg/min every 15 minutes or longer until the desired response is achieved. is guided by frequent measurements, aiming for a controlled reduction—often approximately 25% in within the first hour for severe —while avoiding excessive . Due to its short plasma of about 5 minutes, fenoldopam allows for rapid adjustments during infusion. For pediatric patients (neonates ≥2 kg or full-term to 12 years), the initial dose is 0.2 /kg/min by continuous IV , with increases of 0.3 to 0.5 /kg/min every 20 to 30 minutes until the target is achieved, up to a maximum of 0.8 /kg/min. Therapy is limited to short-term, in-hospital use of up to 48 hours in adults and up to 4 hours in pediatric patients, after which alternative antihypertensive strategies should be considered for maintenance. Continuous monitoring is essential, preferably via an intra-arterial catheter in settings, alongside regular assessments of (to detect dose-related ) and serum levels (due to risk of ). No specific dosage adjustments are required for patients with renal or hepatic impairment, as the drug's clearance is primarily renal but its short minimizes accumulation risks; however, lower starting doses and careful monitoring are recommended in elderly patients due to potential declines in organ function.

Mechanism of action

Fenoldopam is a selective for peripheral D1-like receptors, primarily the D1 subtype, with activity concentrated on vascular cells and renal tubular . It exhibits high affinity for D1 receptors (D1A and D1B subtypes) but lacks significant binding to D2-like receptors, α1- or β-adrenoceptors, or serotonin receptors, while showing only moderate affinity for α2-adrenoceptors. The biologically active R-isomer demonstrates approximately 250-fold greater potency at D1 receptors compared to the S-isomer in the racemic formulation. At the molecular level, fenoldopam binds to D1 receptors, which are G protein-coupled receptors linked to stimulatory G proteins (Gs). This binding activates , leading to increased intracellular (cAMP) levels, which in turn promotes relaxation of vascular through A-mediated and reduced intracellular calcium. The resulting is dose-dependent and primarily affects arterioles in the renal, coronary, mesenteric, and peripheral vascular beds, reducing systemic and without direct inotropic or effects on the heart due to the absence of β-adrenergic activity. In the kidneys, D1 receptor activation enhances renal blood flow, , and natriuresis by dilating both afferent and and inhibiting sodium in the proximal tubules. Unlike non-selective dopamine agonists such as itself, fenoldopam does not stimulate D2 receptors or α-/β-adrenoceptors at therapeutic doses, thereby avoiding effects like or and cardiac stimulation that could increase myocardial oxygen demand. This peripheral selectivity contributes to its profile as a targeted vasodilator for acute management, with minimal impact on presynaptic dopamine autoreceptors or activity.

Pharmacokinetics

Fenoldopam is administered exclusively via intravenous infusion, as it is not suitable for oral use due to extensive first-pass metabolism. Following IV administration, the onset of blood pressure reduction occurs within 4 to 5 minutes, with steady-state plasma concentrations achieved in approximately 20 minutes, proportional to the infusion rate. The drug exhibits rapid distribution, with a volume of distribution of approximately 0.6 L/kg, indicating primarily extracellular distribution. Fenoldopam minimally crosses the blood-brain barrier, with less than 0.005% penetration observed in animal studies. Fenoldopam undergoes extensive metabolism primarily through conjugation processes, including sulfation, , and , occurring in the gut and liver without involvement of enzymes. The major metabolites are inactive sulfated and glucuronidated conjugates. is predominantly renal, with about 90% of the dose eliminated in the as metabolites and 10% in , while only 4% is excreted unchanged. The plasma elimination is short, approximately 5 minutes in adults and 3 to 5 minutes in children, which supports the need for continuous IV to maintain therapeutic effects. In special populations, pharmacokinetics remain largely unchanged. No dose adjustments are required for mild to moderate renal or hepatic impairment, as clearance is unaffected even in end-stage renal disease or severe hepatic failure. In pediatric patients, pharmacokinetics are independent of age when corrected for body weight.

Adverse effects

Common side effects

The most common side effects associated with fenoldopam administration occur in more than 5% of patients and are primarily related to its vasodilatory effects. In clinical trials involving fixed doses in adults with severe , headache was reported in 24% of patients, nausea in 12%, cutaneous dilation (flushing) in more than 5%, and in more than 5%. Reflex , a compensatory response to via activation, is also frequently observed, particularly with higher doses exceeding 0.8 mcg/kg/min. These effects stem from fenoldopam's selective dopamine-1 receptor , which promotes peripheral leading to flushing and , while the resulting drop in triggers reflex . is dose-related and more pronounced with rapid titration. In some cases, dopaminergic stimulation of renal tubules may contribute to mild , though this is less common. Most common side effects are generally mild and self-limiting, resolving upon discontinuation of the infusion. Supportive measures, such as antiemetics for or careful blood pressure monitoring to mitigate , are typically sufficient for management.

Serious adverse effects

Fenoldopam therapy can lead to serious adverse effects, primarily due to its vasodilatory and actions, though these occur infrequently. One key risk is a dose-dependent increase in , with a mean rise of 6.5 mm Hg observed during infusion, potentially exacerbating or precipitating acute angle-closure glaucoma in susceptible patients. This elevation is reversible within approximately two hours after discontinuation but necessitates caution and ophthalmologic monitoring in individuals with pre-existing or . Severe is another significant concern, which may result in tissue ischemia, particularly in patients with compromised , such as those with ; severe may lead to discontinuation of therapy in some patients. Rare hypersensitivity reactions, including , have been reported, often attributable to the preservative in the formulation, which can trigger allergic responses in sulfite-sensitive individuals. Less common but serious events include arrhythmias such as ventricular ectopy and ectopic beats (incidence 0.5-5%), as well as , which may develop within six hours of and requires monitoring. Post-marketing surveillance has identified cases of , though causality is not always established. In elderly patients, severe raises the risk of cerebral hypoperfusion. Overall, these serious effects occur in fewer than 5% of cases, with no evidence of rebound upon abrupt cessation, as returns gradually to baseline. Fenoldopam is approved only for short-term use (up to 48 hours), and long-term safety data are lacking.

Contraindications and precautions

Contraindications

Fenoldopam has no absolute contraindications listed in the FDA prescribing information. However, it should not be used in patients with known to the drug or its components.

Warnings and precautions

The formulation contains , a that may cause severe allergic-type reactions, including or asthmatic episodes, in sulfite-sensitive individuals. Concomitant use of fenoldopam with beta-blockers should be avoided, as beta-blockade may inhibit compensatory , leading to profound . If used together, monitor frequently and consider discontinuing the beta-blocker prior to initiating fenoldopam. Fenoldopam may increase in a dose-dependent manner (mean increase of 6.5 mm Hg). Use with caution in patients with or intraocular hypertension, including untreated narrow-angle glaucoma, and monitor appropriately. Due to its potent vasodilatory effects, fenoldopam requires continuous monitoring of and during to detect and manage or promptly. should be checked in patients with or , as the drug can cause a dose-dependent increase averaging 6.5 mm Hg, which typically resolves within two hours after discontinuation. Electrolyte surveillance, particularly for , is essential, as serum potassium levels may decrease within six hours of starting therapy due to or direct effects. In elderly patients, caution is advised due to potential declines in hepatic, renal, or cardiac function, warranting initiation at the lower end of the dosing range to minimize risk. For individuals with renal impairment, no dosage adjustment is needed as clearance remains unaltered even in end-stage disease, though monitoring for overall hemodynamic stability is recommended given its use to improve renal . In hepatic disease, metabolism is similarly unaffected, but close observation for any unexpected responses is prudent. Fenoldopam may exhibit additive hypotensive effects when combined with other antihypertensives, such as beta-blockers, necessitating frequent monitoring and avoidance of concomitant use where possible to prevent excessive drops from unopposed . No significant interactions occur with ACE inhibitors or . Fenoldopam is classified as B. Animal reproduction studies have failed to reveal evidence of fetal harm, and there are no adequate and well-controlled studies in women. It should be used during pregnancy only if clearly needed. Risk summary: It is unknown whether fenoldopam is excreted in human milk. Fenoldopam is present in rat milk. Because many drugs are excreted in milk and because of the potential for serious adverse reactions in nursing infants from fenoldopam, a decision should be made to discontinue or to discontinue the drug, taking into account the importance of the drug to the mother.

Society and culture

Fenoldopam was approved by the U.S. (FDA) on September 23, 1997, for the short-term management of severe in hospitalized patients when rapid but reversible reduction in is needed. It is available only by prescription and is not classified as a under the , as it has no potential for abuse or dependence. Internationally, fenoldopam has received approval in several European countries for the management of severe , though it lacks centralized authorization from the (EMA). It is not approved for use in by . The drug is assigned the Anatomical Therapeutic Chemical (ATC) classification code C01CA19, within the group of adrenergic and agents. It is not scheduled under any international controlled substances conventions. Generic fenoldopam mesylate injection has been available since the early following the expiration of the original for the brand-name product Corlopam, with the first FDA approvals for generic versions granted in 2003. As of 2025, fenoldopam's regulatory approvals remain unchanged, with no new indications authorized and ongoing monitoring in place; however, all formulations have faced manufacturing discontinuation since 2023, resulting in ongoing shortages, with no resupply planned as of 2025.

Brand names and availability

Fenoldopam is marketed under the brand name Corlopam. The original brand formulation was developed and approved under NDA 19-922 by Inc., which was later acquired by . Generic versions of fenoldopam mesylate injection were produced by several manufacturers in the United States, including Bedford Laboratories, Pharmaforce Inc., and Teva Parenteral Medicines Inc. These generics were supplied in single-dose vials at a concentration of 10 mg/mL, typically in 1 mL (10 mg) or 2 mL (20 mg) volumes, intended for dilution prior to intravenous administration. As an intravenous-only requiring a prescription, fenoldopam was restricted to use and unavailable over-the-counter. , all presentations of Corlopam and generic fenoldopam mesylate injection were discontinued by () in 2023, rendering the drug commercially unavailable in the market. Prior to full discontinuation, intermittent shortages occurred throughout the 2020s, attributed to manufacturing constraints and disruptions. Globally, fenoldopam remains limited to hospital pharmacies in certain countries where intravenous formulations are still distributed, though widespread availability has diminished following the U.S. market exit.

References

  1. https://go.drugbank.com/drugs/DB00800
  2. https://www.ncbi.nlm.nih.gov/books/NBK526058/
  3. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019922s016lbl.pdf
  4. https://www.nejm.org/doi/full/10.1056/NEJMra010253
  5. https://www.mayoclinic.org/drugs-supplements/fenoldopam-intravenous-route/description/drg-20311132
  6. https://www.ashp.org/drug-shortages/current-shortages/drug-shortage-detail.aspx?id=64
  7. https://www.ashp.org/drug-shortages/current-shortages/drug-shortages-list
  8. https://academic.oup.com/ajh/article/12/7/653/112360
  9. https://ccforum.biomedcentral.com/articles/10.1186/s13054-015-1166-4
  10. https://www.ahajournals.org/doi/10.1161/circulationaha.104.509141
  11. https://reference.medscape.com/drug/corlopam-fenoldopam-342399
  12. https://www.ahajournals.org/doi/10.1161/HYP.0000000000000249
  13. https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/19922se5-005_colopam_lbl.pdf
  14. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/019922s019lbl.pdf
  15. https://www.sciencedirect.com/topics/neuroscience/fenoldopam
  16. https://labeling.pfizer.com/ShowLabeling.aspx?id=4445
  17. https://www.drugs.com/sfx/fenoldopam-side-effects.html
  18. https://www.drugs.com/monograph/fenoldopam.html
  19. https://www.rxlist.com/fenoldopam/generic-drug.htm
  20. https://nursing.unboundmedicine.com/nursingcentral/view/Davis-Drug-Guide/51299/all/fenoldopam
  21. https://pubmed.ncbi.nlm.nih.gov/9115057/
  22. https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/019922_toc.cfm
  23. https://atcddd.fhi.no/atc_ddd_index/?code=C01CA19&showdescription=no
  24. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/076656Orig1s000.pdf
  25. https://www.drugs.com/availability/generic-corlopam.html
  26. https://www.pfizerhospitalus.com/product/00409-3373-02
  27. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/077826Orig1s000.pdf
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