Fenoldopam (Monograph)

Brand name: Corlopam
Drug class: Central alpha-Agonists

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Benzazepine-derivative vasodilating agent.^{1 10 11 12}

Uses for Fenoldopam

Hypertension

Used for short-term (up to 48 hours), in-hospital 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, hypertensive emergencies).^{1 10 1200} 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), in-hospital management of hypertension in pediatric patients.¹ Some experts state fenoldopam may be used for the management of acute severe hypertension in pediatric patients without life-threatening symptoms in whom oral therapy is not appropriate.¹¹⁵⁰

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

• Adjust dosage according to BP until target BP is reached.¹

• May abruptly discontinue fenoldopam infusion¹⁴ or gradually taper prior to discontinuance of therapy.^{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.

IV Administration

Administer by continuous IV infusion.¹

Dilution

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

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

Infusion 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 fenoldopam concentration of 60 mcg/mL.¹

Infusion 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 fenoldopam 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.¹ (See Dosage: Pediatric Patients under Dosage and Administration)

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

Dosage

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

Pediatric Patients

Hypertension

IV

In-hospital, short-term (≤4 hours) BP reduction: Initially, 0.2 mcg/kg per minute by IV infusion recommended by manufacturer.¹ May increase dosage every 20–30 minutes by up to 0.3–0.5 mcg/kg per minute to a maximum dosage of 0.8 mcg/kg per minute.¹

Acute severe hypertension without life-threatening symptoms: Some experts suggest a dosage of 0.2–0.5 mcg/kg per minute by IV infusion, which may be titrated up to 0.8 mcg/kg per minute if necessary.¹¹⁵⁰ Reduce BP in such patients by ≤25% of the planned reduction over the first 8 hours, with remainder of reduction over next 12–24 hours.¹¹⁵⁰

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: 0.01–0.3 mcg/kg per minute.^{1 12 14 1200} To achieve desired therapeutic effect, may titrate dosage upward in increments of 0.05–0.1 mcg/kg per minute^{1 14} no more frequently than every 15 minutes until target BP is reached.¹

Lower initial dosages (<0.1 mcg/kg per minute) titrated slowly have been associated with less reflex tachycardia.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

Hypertensive emergency in adults with a compelling indication (severe preeclampsia or eclampsia, pheochromocytoma crisis): Reduce SBP to <140 mm Hg during the first hour.¹²⁰⁰

Hypertensive emergency in adults with a compelling indication (acute aortic dissection): Reduce SBP to <120 mm Hg within the first 20 minutes.¹²⁰⁰

Hypertensive emergency in adults without a compelling indication: Reduce SBP by ≤25% within first hour, followed by further BP reduction if stable to 160/100 or 160/110 mm Hg within the next 2–6 hours; avoid excessive declines in BP that could precipitate renal, cerebral, or coronary ischemia.^{542 1200} If this BP is well tolerated and the patient is clinically stable, may implement further gradual reductions toward normal BP in the next 24–48 hours.¹²⁰⁰

Prescribing Limits

Pediatric Patients

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 used in clinical trials.¹ Maintenance infusions may be continued for up to 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

• Some experts state the drug is contraindicated in patients at risk of increased IOP (i.e., glaucoma) or intracranial pressure and in those with a sulfite allergy.¹²⁰⁰

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 adults receiving infusion rates >0.1 mcg/kg per minute and in pediatric patients receiving infusion rates >0.8 mcg/kg per minute.¹ In adults, tachycardia may diminish over time with continued therapy at dosages of fenoldopam <0.1 mcg/kg per minute.¹

ECG T wave inversion, extrasystoles, palpitations, cardiac failure, ischemic heart disease, and angina pectoris reported during clinical trials with fenoldopam.¹

Hypokalemia

Decreases in serum potassium reported after <6 hours of fenoldopam infusion.¹ Monitor serum potassium concentrations.¹

Intraocular Pressure (IOP)

Dose-dependent, reversible increases in IOP reported in patients with glaucoma or ocular hypertension.^{1 10 14}

Specific Populations

Pregnancy

Category B.¹

Fetal harm not observed in animal reproductive studies with fenoldopam; however, reproductive studies in humans lacking.¹ Use during pregnancy only if clearly needed.¹

Lactation

Distributed into milk in rats; not known whether distributed into human milk.¹ Discontinue nursing or the drug.¹

Pediatric Use

Antihypertensive effects of fenoldopam evaluated in pediatric patients (age <1 month [≥2 kg or full term] to 12 years) requiring BP reduction.¹

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

Headache,^{1 10 11 12 14} cutaneous dilation (flushing),^{1 10 11 12 14} nausea,^{1 12 14} hypotension.^{1 12}

Drug Interactions

Not metabolized by CYP isoenzymes.¹

Specific Drugs

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 in rats.^{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 Data lacking on effects of hemodialysis on pharmacokinetics of fenoldopam.¹

Stability

Storage

Parenteral

Injection

2–30°C.¹

Ampuls and vials 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

Parenteral

Solution CompatibilityHID

Drug CompatibilityHID

Actions

• Rapid-acting vasodilator.^{1 10 12 14}

• 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

• 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 Cl_cr observed in patients with severe hypertension, including those with renal impairment.^{10 11 13 14}

Advice to Patients

• Importance of advising patients with underlying hypertension that they require continued follow-up for their medical condition and that they should continue taking their oral antihypertensive drug(s) as directed.¹

• Importance of advising patients to contact a healthcare professional immediately if they develop signs and symptoms of a new hypertensive emergency (e.g., neurologic symptoms, visual changes, evidence of CHF).¹

• 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.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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