Fenoldopam Mesylate: Uses, Dosage, Precautions, Side Effects, and Pharmacological Aspects

Overview

Fenoldopam mesylate, an intravenous vasodilator (used to widen the blood vessels), emerged as a crucial intervention for managing hypertension, particularly in situations where oral therapy is not viable. After completing pivotal trials, the United States Food and Drug Administration (USFDA) approved Fenoldopam mesylate in December 1997. Its unique position extends to treating severe hypertension (high blood pressure), encompassing cases with or without associated target-organ damage. By targeting specific receptors, this medication effectively promotes vasodilation and improves blood flow, making it a valuable option when rapid and precise blood pressure control is imperative.

Drug Group

Fenoldopam is classified as a selective dopamine-1 (D1) receptor agonist. It belongs to the pharmacological class of drugs known as vasodilators. The primary therapeutic use of Fenoldopam mesylate is for the short-term intravenous (through the vein) treatment of severe hypertension in a hospital setting. It works by selectively activating dopamine-1 receptors, leading to vasodilation and a subsequent reduction in blood pressure.

Indications

The indications for Fenoldopam mesylate are

• Adults Patients: Fenoldopam mesylate is prescribed for the in-hospital, short-term (up to 48 hours) control of severe hypertension when there is a clinical need for a rapid yet readily reversible emergency reduction in blood pressure. This includes cases of malignant hypertension with declining end-organ function. Transition to oral therapy using an alternative agent can be initiated once the blood pressure has stabilized following Fenoldopam infusion.

• Pediatric Patients: For pediatric patients, Fenoldopam mesylate is recommended for in-hospital, short-term (up to four hours) lowering of blood pressure.

Dosage Forms and Available Strengths

Available in the following dosage forms and strengths:

• Solution in Single-Dose Vial: 10 mg/mL (milligram per milliliter).

• Solution in Single-Dose Ampule: 10 mg/mL.

Warnings and Precautions

The associated warnings and precautions are:

• Tachycardia: Fenoldopam mesylate can make the heart beat faster, especially when the infusion rate is high in adults or kids. If the dose is kept below certain levels, the fast heart rate in adults might go away with continued treatment.

• Hypokalemia: After using Fenoldopam for less than six hours, there is a chance of low potassium levels. This can happen due to the drug's effect on how the body handles potassium and sodium. It is necessary to monitor potassium levels in the blood.

• Increased Intraocular Pressure: In a study with people with eye issues, Fenoldopam raised the pressure inside the eye, but it returned to normal within two hours of stopping the drug.

• Allergic Reactions Associated With Sulfite: Fenoldopam includes an ingredient known as Sodium metabisulfite, which may lead to allergic reactions in certain individuals, especially those with asthma (airway obstruction caused by lung inflammation). The chances of having an issue with it are not very common, but it is more likely in people with asthma.

For Patients

What Does Hypertensive Emergency Mean?

A hypertensive emergency occurs when blood pressure rises dangerously high, posing an immediate risk of severe organ damage. It requires urgent medical intervention to bring blood pressure under control and prevent complications. Symptoms may include a severe headache, chest pain, and confusion. It is necessary to seek emergency care in the event of a hypertensive emergency.

How Does the Fenoldopam Mesylate Work?

Fenoldopam mesylate works by selectively stimulating dopamine-1 receptors, leading to vasodilation. This helps lower blood pressure (BP) and improve blood flow, making it effective in hypertensive emergencies and supporting kidney function.

What Are the Clinical Uses of the Fenoldopam Mesylate?

Fenoldopam mesylate is primarily used for its vasodilatory properties and is clinically employed in the following situations:

• Hypertensive Emergencies: Fenoldopam is used to manage hypertensive emergencies, where rapid and controlled blood pressure reduction is necessary to prevent organ damage.

• Postoperative Hypertension: It may address elevated blood pressure following surgical procedures.

• Cardiac Surgery: Fenoldopam can be employed in cardiac surgery to promote kidney function and prevent or manage renal impairment.

What Is the Dosage of the Fenoldopam Mesylate?

Start intravenous Fenoldopam mesylate at 0.01 to 0.3 mcg/kg/min (micrograms per kilogram per minute); adjust every 15 minutes, not exceeding 1.6 mcg/kg/min. Lower doses and gradual titration may reduce reflex tachycardia (rapid heartbeat). Maintenance infusions can last up to 48 hours. Oral antihypertensives can be added during or after Fenoldopam. For pediatric patients, initiate at 0.2 mcg/kg/minute, titrate by 0.3 to 0.5 mcg/kg/min every 20 to 30 minutes, with a maximum dose of 0.8 mcg/kg/minute. Higher doses may not further decrease mean arterial pressure but can worsen tachycardia.

How Is Fenoldopam Mesylate Administered?

Fenoldopam mesylate is administered in a hospital setting. The doctor or the nurse will mix the content of ampoules or vials with 0.9 percent Sodium chloride or five percent dextrose in water before using. Each ampule or vial is for one use only. Discard if not used in the fridge within four hours at room temperature or 24 hours. It is crucial to check for any particles or color changes before using; discard if seen.

1. Dilution for Adults:

• 4 mL or milliliter (40 mg) in 1000 mL (milliliter) gives 40 mcg/mL (micrograms per milliliter).

• 2 mL (20 mg) in 500 mL gives 40 mcg/mL.

• 1 mL (10 mg) in 250 mL gives 40 mcg/mL.

2. Dilution for Children:

• 3 mL (30 mg) in 500 mL gives 60 mcg/mL.

• 1.5 mL (15 mg) in 250 mL gives 60 mcg/mL.

• 0.6 mL (6 mg) in 100 mL gives 60 mcg/mL.

To calculate infusion rate (mL/h):

Infusion Rate = Dose (mcg/kg/min) x weight (kg) x 60 divided by the concentration (mcg/mL).

Example:

• For a 132.28 pounds (60 kg) patient at 0.01 mcg/kg/min with a 40 mcg/mL concentration: Infusion rate = 0.01 × 60 × 60 divided by 40 (concentration) = 0.9 mL/h (milliliters per hour).

• For a 22.05 pounds (10 kg) patient at 0.2 mcg/kg/min with a 60 mcg/mL concentration: Infusion rate = 0.2 × 10 × 60 divided by 60 (concentration) = 2.0 mL/h.

What Are the Side Effects of Fenoldopam Mesylate?

Fenoldopam mesylate, a medication primarily used for the short-term treatment of severe hypertension, may have side effects. Common side effects include:

• Cardiovascular:

  • Flushing.

  • Hypotension (low blood pressure).

  • Tachycardia.

  • Chest pain.

  • Bradycardia (low heart rate).

  • ST-T abnormalities.

  • Irregular heartbeats.

  • Myocardial infarction (heart attack).

  • Orthostatic hypotension (a sudden drop in blood pressure upon standing).

  • Palpitations.

• Central Nervous System:

  • Headache.

  • Anxiety (excessive worry).

  • Dizziness.

  • Insomnia (a sleep disorder characterized by lack of sleep).

• Dermatologic:

  • Diaphoresis (excessive sweating).

• Endocrine and Metabolic:

  • Hyperglycemia (elevated blood glucose levels).

  • Hypokalemia (low levels of potassium in the blood).

  • Increased lactate dehydrogenase levels.

• Gastrointestinal:

  • Nausea.

  • Abdominal pain.

  • Constipation.

  • Diarrhea.

  • Vomiting.

• Genitourinary:

  • Decreased urine output.

  • Urinary tract infection.

• Hematologic and Oncologic:

  • Hemorrhage (excessive bleeding).

  • High white blood cell count.

• Hepatic:

  • Increased serum transaminases.

• Neuromuscular and Skeletal:

  • Myalgias (muscle pain).

• Ophthalmic:

  • Increased intraocular pressure.

• Renal:

  • Increased BUN (blood urea nitrogen).

• Increased serum creatinine.

• Respiratory:

  • Difficulty breathing.

  • Nasal congestion.

• Constitutional:

  • Fever.

What Are the Things to Inform the Doctor Before Taking Fenoldopam Mesylate?

Before taking Fenoldopam mesylate, inform the doctor about:

• Medical history, including heart or kidney issues.

• Current medications, including over-the-counter drugs and supplements.

• Allergies to medications.

• Pregnancy or breastfeeding status.

• Blood pressure levels.

• Scheduled surgeries or dental procedures.

• Conditions causing fluid or electrolyte imbalances.

• Previous adverse reactions to Fenoldopam mesylate.

• Other medical conditions, such as diabetes (increased sugar in the blood) or lupus (autoimmune disorder).

Dietary Considerations

No diet modification is needed. Adhere to the doctor's guidance regarding food, drink, or physical activity limitations.

Missed Dose

As Fenoldopam is administered continuously during emergencies, the likelihood of missing a dose is minimal.

Overdose

In the event of a Fenoldopam overdose, the anticipated reaction is likely to involve severe low blood pressure. This should be addressed by discontinuing the medication and implementing suitable supportive measures.

Storage, Handling, and Disposal

Fenoldopam mesylate is stored in a container with a concentration of 10 mg/mL.

Fill Quantity (Per Carton):

• Single-dose vials, 1 mL (milliliter).

• Single-dose vials, 2 mL.

• Single-dose ampule, 1 mL.

• Single-dose ampule, 2 mL.

It must be stored between two to 30 degrees Celsius (35.6 to 86 degrees Fahrenheit). For disposal, use specific methods to eliminate unnecessary Fenoldopam mesylate, like a medicine take-back program. For information on such programs, speak with the local recycling and waste management department or the pharmacist.

For Doctors

Chemical Taxonomy

Fenoldopam mesylate injection, USP (United States Pharmacopeia), is a dopamine D1-like receptor agonist. It is designed as a solution intended to dilute intravenous infusions.

Chemically identified as 6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-[1H]-3-benzazepine-7,8-diol methane sulfonate,

The following structure represents Fenoldopam mesylate:

Fenoldopam mesylate is a white to off-white powder, possessing a molecular weight of 401.87 and a molecular formula represented as C16H16ClNO3•CH3SO3H. It exhibits limited solubility in water, ethanol, and methanol while soluble in propylene glycol.

Dose:

• For Adults: Start with an intravenous infusion at 0.01 to 0.3 mcg/kg/min (micrograms per kilogram per minute), adjusting every 15 minutes or longer until normal or targeted blood pressure is achieved, with a maximum of 1.6 mcg/kg/min. Lower doses and slow increases reduce reflex heart rate increases. The patient can continue the infusion for up to 48 hours; other oral medications can be added during or after.

• For Kids: Begin with 0.2 mcg/kg/min and adjust by 0.3 to 0.5 mcg/kg/min every 20 to 30 minutes, but do not exceed 0.8 mcg/kg/minute. Higher doses do not lower blood pressure more but may increase heart rate.

What Are the Pharmacological Actions of Fenoldopam Mesylate?

The pharmacological actions of Fenoldopam mesylate are

1. Pharmacodynamics:

In mild to moderate hypertension (32 patients), Fenoldopam infusion yielded a dose-dependent blood pressure reduction over 48 hours. Tolerance was noted at higher doses. Hypertensive emergencies (94 adults) showed dose-related blood pressure reduction and increased heart rate with 0.01-0.3 mcg/kg/min infusions for 24 hours. In severe hypertension (236 adults), Fenoldopam had a 79 percent response rate comparable to Nitroprusside. The pediatric study (77 patients) demonstrated effective blood pressure reduction at 0.2 mcg/kg/min, plateauing at 0.8 mcg/kg/min. Higher doses worsened tachycardia, with effects noticeable within five minutes, lasting up to four hours. Discontinuation led to baseline values.

2. Mechanism of Action: Fenoldopam acts swiftly as a vasodilator, targeting D1-like dopamine receptors and alpha2-adrenoceptors. It lacks significant affinity for D2-like receptors, alpha1 and beta-adrenoceptors, 5HT1 and 5HT2 receptors, or muscarinic receptors. The R-isomer, with higher D1-like receptor affinity, is responsible for its biological activity. In preclinical studies, Fenoldopam does not act on presynaptic D2-like dopamine receptors or alpha- or beta-adrenoceptors and does not impact angiotensin-converting enzyme activity. Fenoldopam may elevate norepinephrine plasma concentration.

3. Pharmacokinetics:

• For Adult Patients: Fenoldopam, infused continuously, reaches a steady state in 20 minutes, unaffected by age, gender, or race. There are no formal drug interaction studies; clearance is unaffected in renal or hepatic issues, but the impact of hemodialysis is unknown.

• For Pediatric Patients: In children aged one month to 12 years, steady-state Fenoldopam plasma concentrations are dose-proportional (0.05 mcg/kg/min to 3.2 mcg/kg/min). The elimination half-life is three to five minutes, and clearance is 3 L/h/kg (liters per hour per kilogram).

• Excretion and Metabolism: About 90 percent of infused Fenoldopam is eliminated in the urine, with only four percent excreted unchanged. Elimination involves conjugation processes (methylation, glucuronidation, and sulfation), with no significant involvement of cytochrome P-450 enzymes. Animal studies suggest that the metabolites are inactive.

Non-clinical Toxicity

Studies for testing the toxic effects of Fenoldopam were conducted on animal models (mice and rats) to see if the drug could cause cancer, mutations, or affect fertility.

In Animal Models:

• Animal models were given different doses of Fenoldopam for 24 months.

• No increase in cancer was observed.

• Some bone-related issues and kidney inflammation were documented in high-dose groups but not cancer.

For Fertility:

• Animal studies also showed that when given orally, Fenoldopam did not affect fertility or reproductive performance.

In Laboratory Tests:

• Fenoldopam did not cause gene mutations in bacteria or mammalian cells.

• There were some chromosome abnormalities in a cell test, but no such issues were found in living animal tissues.

What Are the Contraindications of Fenoldopam Mesylate?

None.

What Are the Drug Interactions of Fenoldopam Mesylate?

The drug interactions include:

• Beta-Blockers: Do not use Fenoldopam concurrently with beta-blockers. If these medications are used together, closely monitor blood pressure, as beta-blockers may inhibit the sympathetic reflex response to Fenoldopam, potentially leading to hypotension (low blood pressure).

Clinical Studies

Fenoldopam mesylate was tested in two hundred thirty-six (236) adults with severe hypertension, a condition in which diastolic blood pressure greater than or equal to 120 mmHg (millimeters of mercury) was randomly assigned to Fenoldopam or Nitroprusside in two studies. Response rates were 79 percent and 77 percent, respectively. Response criteria included lowering diastolic blood pressure to less than 110 mmHg for a baseline of 120 to 150 mmHg or by more than or equal to 40 mmHg for a baseline of more than 150 mmHg. Fenoldopam doses ranged from 0.1 to 1.5 mcg/kg/min, and Nitroprusside doses from one to eight mcg/kg/min. Most observed effects at one hour were present at 15 minutes. Any additional impact after one hour was consistent across all groups and may not be drug-related (no placebo group).

Use in Specific Populations

• Pregnancy: Fenoldopam is a pregnancy category B, which means it is not recommended during pregnancy. Animal studies showed no harm to fetuses, but higher doses caused maternal toxicity. While no evidence of fertility issues exists, caution is advised. Use in pregnant women only if necessary due to the lack of well-controlled studies.

• Nursing Mothers: Fenoldopam is found in rat milk, but it is uncertain if this happens in humans. Given that many drugs can pass into human milk, it is advisable to stop nursing or Fenoldopam use.

• Pediatric Use: Fenoldopam is considered safe and effective for blood pressure reduction in children aged less than one month (at least 4.41 pounds (2 kg) or full term) to 12 years old. The side effects in kids are similar to those in adults. The impact of Fenoldopam on long-term growth and development has yet to be studied.

• Geriatric Use: Fenoldopam studies lack sufficient participants aged 65 and over. Though reported experiences show no significant differences, a lower initial dose is advised for the elderly due to potential variations in organ function, health conditions, or medications.