Furosemide - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

Overview:

Furosemide is a drug used to treat high blood pressure and control edema. It is available as an oral tablet and injection (to be administered by a healthcare professional only). Furosemide acts by increasing urine output. Avoid exposure to direct sunlight while taking this drug, as it can result in sensitivity. If symptoms of severe skin reactions or flu-like symptoms, spreading red rash, or skin/mucous membrane blistering is experienced, stop using the drug and report to the doctor immediately.

Furosemide is classified under the class of medications called loop diuretics (also called water pills). The drugs of this class act by eliminating the excess fluid in the body through the kidneys. The other drugs in the loop diuretic class include Torsemide, Bumetanide, Ethacrynic Acid, etc.

Furosemide has been approved by the Food and Drug Administration (FDA) for treating edema due to congestive heart failure and renal failure, including nephrotic syndrome or liver failure.

The doctors must be aware of Furosemide's indications and administration to reduce adverse effects and ensure safe practices.

For Patients:

What Is Furosemide Used For?

Furosemide is used to treat the following conditions:

• High Blood Pressure: It is a condition characterized by an increase in the force by which the blood is pushed too hard against the artery walls. Many times, high blood pressure goes unnoticed. Left untreated, it can eventually lead to heart disease and stroke.

• Edema: Edema is the fluid accumulation in the bodily tissues that results in swelling. Edema can affect any body area, although it tends to manifest more visibly in the hands, arms, feet, ankles, and legs.

• Chronic Kidney Disease: It refers to longstanding kidney disease resulting in the buildup of waste materials in the body.

Never use Furosemide or any other medication without talking to the doctor first.

How Does Furosemide Work?

Furosemide increases the urine flow by acting on the kidneys, which is beneficial in conditions like edema, congestive heart failure, and chronic kidney disease. High blood pressure reduces the workload on the arteries and the heart.

Onset Of Action:

About 59 % to 64 % of the orally administered Furosemide is absorbed and reaches the blood circulation. The maximum concentration in the blood is reached within 50 to 90 minutes after administration. Furosemide is primarily excreted through kidneys and about seven to nine percent through feces.

In short, the onset of action of Furosemide is within one hour, and the effect lasts about eight hours.

Habit-Forming:

Furosemide is reported to be habit-forming on longer use. Hence, using the medication only as directed by the physician. Avoid sharing the medicine with others and abruptly stop the drug. Talk to the doctor for all the directions regarding drug use.

Expiry Date:

Avoid using tablets past their expiration date, which will be provided at the back of the drug packet.

What Is the Dosage of Furosemide?

The doctor will determine the dose of Furosemide based on the patient's condition, age, sex, and weight. It is important to regularly follow up with the doctor at the scheduled times to assess the response to the drug. Report to the physician if any side effects are experienced.

Furosemide is available in the following dosage forms:

• Injection Solution: 10 mg/ml.

• Oral Tablet: 20 mg, 40 mg, 80 mg.

The general dosing information of Furosemide is as follows:

1. High Blood Pressure:

• Adult Dosing: 80 mg orally daily, along with other drugs.

2. Edema:

• Adult Dosing: 20 to 80 mg orally as a single dose which will be adjusted by the doctor based on the response.

• Child Dosing: 2 mg/kg orally as a single dose; may increase by 1 to 2 mg/kg no sooner than 6 to 8 hours following the previous dose.

3. Chronic Kidney Disease:

• Adult Dosing: 40 mg IV bolus with or without albumin 20 % 10 mg IV bolus.

• Child Dosing: 2 mg/kg orally as a single dose; may increase by 1 to 2 mg/kg no sooner than 6 to 8 hours following the previous dose.

How to Use Furosemide?

• Take the medication by mouth with a glass of water.

• It is usually prescribed to be administered in the morning to avoid sleeping disturbance due to increased urination while taking the drug.

• Furosemide can cause sun sensitivity. Use sunscreens or protective clothing while taking this drug.

• Consumption of potassium-rich food is encouraged for patients taking this medication.

• In case of queries, contact the doctor or the pharmacist.

Missed Dose:

In case of a missed dose, it can be taken when the patient remembers. However, if it is almost time for the coming dose, skip the previous dose and continue with the regimen. Avoid taking double doses to catch up on the missed one.

Overdose:

In case of an overdose and serious symptoms arise, seek medical help or contact the emergency department immediately.

What Are the Drug Warnings and Precautions?

Inform the doctor if any of the following conditions are present:

• Infants: Heart-related complications are reported when Furosemide is administered to premature infants in the first week of pregnancy.

• Diabetes: Furosemide may increase blood sugar levels. Monitoring of blood sugar levels is required in patients with diabetes.

• Electrolyte Imbalance: Furosemide can alter the electrolyte balance in the body. Inform the doctor if any of the electrolytes are elevated or declined from the normal range, especially if there is a variation in the sodium, potassium, calcium, or magnesium levels. The doctor may advise a diet with restricted salt intake.

• Liver Diseases: Furosemide can worsen liver function in patients with pre-existing liver diseases. Talk to the doctor before taking the medication.

• Kidney Diseases: Kidney function should be regularly monitored while on therapy with Furosemide, as the disease condition may worsen.

• Elderly: Patients above the age of 65 are at an increased risk of dehydration.

• Pregnancy and Breastfeeding: Talk to the doctor before taking the drug if pregnant or breastfeeding.

What Are the Side Effects of Furosemide?

The common side effects include

• Increased uric acid levels.

• Decreased magnesium levels.

• Loss of appetite.

• Bladder spasm.

• Dizziness.

• Blurred vision.

Avoid activities requiring coordination or mental alertness due to these side effects. Inform the doctor if these signs and symptoms worsen or the condition worsens.

The more severe side effects include

• Sudden decline in blood pressure while changing positions (standing after sitting or lying down for a long period).

• Severe allergic reactions to the medication are characterized by symptoms like rashes, itching, hives, breathlessness, etc.

• Inflammation of the pancreas.

If these effects occur, seek emergency medical help.

For Doctors:

Indications:

Furosemide has been approved by the Food and Drug Administration (FDA) to treat conditions like edema secondary to congestive heart failure exacerbation, renal failure, nephrotic syndrome, or liver failure.

In acutely decompensated heart failure (ADHF) patients with volume overload where diuretics were not administered previously. The starting dose of Furosemide must be 20 to 40 milligrams intravenously.

However, for patients with acutely decompensated heart failure (ADHF) with a normal kidney function on diuretic therapy, the starting dose of Furosemide can be equal to or greater than the total oral dose of Furosemide the patient takes daily.

Further, the diuretic dose is adjusted according to the patient's clinical response.

An improvement in the patient's symptoms is reported if the starting doses of Furosemide are higher (two and a half times the total daily oral dose of Furosemide).

Diuretic therapy can be administered in patients with ascites and liver cirrhosis, but dietary sodium intake is restricted. The recommended diuretics are a combination of Furosemide and Spironolactone with an initial ratio of 40 milligrams of Furosemide and 100 milligrams of Spironolactone. This dose can be increased in increments of the same ratio, a maximum dose of 400 milligrams of Spironolactone and 160 milligrams of Furosemide. However, the diuretics doses are relatively low (50 milligrams of Spironolactone with 20 milligrams of Furosemide) in patients with intolerance to diuretics secondary to borderline blood pressure.

Mechanism of Action

Furosemide acts by inhibiting the reabsorption of tubular sodium and chloride in the kidney's proximal and distal tubules and Henle's thick ascending loop. It further stops the co-transportation of the sodium-chloride system, causing water excretion, including sodium, chloride, calcium, and magnesium.

Pharmacokinetics

Absorption: Furosemide starts acting within the first hour of oral administration. The peak effect is achieved within one to two hours. In patients with edema, the Furosemide absorption is slower than normal, especially in patients with decompensated heart failure, but the loop diuretic absorption is normal.

Bioavailability: The mean bioavailability of Furosemide (oral) is 51 percent compared with the bioavailability of Furosemide (intravenous).

Furosemide administered orally and sublingually shows a peak concentration slower than the intravenous route. The bioavailability of Furosemide varies and is relatively less than that of Torsemide in patients with compensated congestive heart failure.

Distribution: In otherwise healthy people, more than 95 percent of Furosemide binds to plasma protein (albumin). Only 2.3 to 4.1 percent of Furosemide exists in an unbound form in therapeutic concentrations.

Metabolism: Furosemide glucuronide is the main biotransforming active product of Furosemide, with an active diuretic effect. Recent evidence shows that Furosemide is metabolized minimally in the liver.

Excretion:

• Terminal Half-Life: Approximately two hours (prolonged in patients with chronic renal disease).

• Total Time of Therapeutic Effect: 6 to 8 hours.

Administration:

Furosemide is available in the following formulations

• Oral (tablets and solutions).

• Intravenous.

Intravenous Furosemide shows double potency than oral Furosemide.

In patients with adequate renal function, the oral dose of Furosemide equivalent to other oral diuretics is as follows:

• 40 mg of Furosemide = 1 mg of Bumetanide = 20 mg of Torsemide

Furosemide oral tablets are available in 20 mg, 40 mg, and 80 mg.

Furosemide oral solution is available as 8 mg/ml or 10 mg/ml (40 mg Furosemide per 5 ml solution).

Breaking Phenomenon:

Increased sodium excretion in urine occurs when an individual receives oral or intravenous Furosemide. The first dose of this medication leads to substantial sodium excretion and diuresis within the first three to six hours. When the effect of Furosemide wears off, the kidney causes sodium and chloride retention. This is known as post-diuretic sodium retention. Therefore, it is recommended to repeat the Furosemide dose at six to eight hours to achieve significant diuresis and avoid post-diuretic sodium retention.

When the Furosemide dose becomes chronic in a patient, there is shrinkage of extracellular fluid volume, and the level of natriuresis (excretion of sodium in the urine) decreases. At this point, the amount of natriuresis becomes equal to sodium intake, known as the breaking phenomenon.

Use in Specific Population:

1. Pregnancy Considerations: Furosemide is considered a pregnancy category C drug under the old FDA categories. This medication must be administered with caution in pregnant women, and the risks and benefits must be informed to the patient. Furosemide can cross the placenta, and studies in animal reproduction have caused adverse effects. However, Furosemide has been used in pregnant women with heart failure after carefully considering the risks and benefits and taking the required precautions. In addition, close monitoring of fetal growth is necessary.

2. Patients with Hepatic Impairment: Furosemide therapy should be initiated in the hospital in patients with hepatic cirrhosis and ascites. In the case of hepatic coma and electrolyte depletion, the medication must not be initiated once the underlying condition is improved.

3. Patients with Renal Impairment: If the glomerular filtration rate (GFR) is less than or equal to 30 mL/min, the doses must be increased to achieve the desired diuretic response. If increasing azotemia (elevation of nitrogenous products in the blood) and oliguria (low urine output) are seen while treating serious progressive renal disease, Furosemide must be discontinued.

4. Breastfeeding Considerations: There is limited data on using Furosemide during breastfeeding. As intense diuresis may decrease lactation, an alternate medicine must be used, particularly while nursing a newborn or preterm infant. However, low doses of Furosemide might not suppress lactation.

Adverse Effects:

Adverse reactions are classified according to the system affected. The following are adverse effects associated with using Furosemide:

Gastrointestinal System

• Hepatic encephalopathy in patients with cirrhosis.

• Jaundice (intrahepatic cholestatic jaundice).

• Pancreatitis.

• Elevation of liver enzymes.

• Anorexia.

• Oral and gastric irritation.

• Cramping.

• Constipation.

• Nausea and vomiting.

Systemic Hypersensitivity Reactions

• Severe anaphylactic or anaphylactoid reactions (shock).

Central Nervous System:

• Ototoxicity.

• Paresthesias.

• Dizziness.

• Xanthopsia.

• Headache.

• Vertigo.

• Blurred vision.

Hematologic Reactions

• Thrombocytopenia.

• Aplastic anemia.

• Agranulocytosis.

• Hemolytic anemia.

• Anemia.

• Eosinophilia.

• Leukopenia.

Dermatologic-hypersensitivity Reactions:

• Toxic epidermal necrolysis.

• Erythema multiforme.

• Drug rash with eosinophilia and systemic symptoms.

• Exfoliative dermatitis.

• Acute generalized exanthematous pustulosis.

• Bullous pemphigoid.

• Purpura.

• Rash.

• Photosensitivity.

• Urticaria.

• Pruritus.

Cardiovascular System:

• Alcohol, narcotics, or barbiturates may cause orthostatic hypotension.

• Elevated cholesterol and triglyceride serum levels.

Renal Disorders:

• Acute kidney injury due to fluid loss.

Metabolic Disorders

• Hyperglycemia.

• Hyperuricemia.

• Hypokalemia.

• Hypomagnesemia.

Contraindications:

Do not use Furosemide under the following conditions:

• History of drug allergy to the active or inactive components of Furosemide.

• In patients with anuria (a condition where kidneys fail to produce urine).

• Along with the drug Desmopressin, Ethacrynic acid, and drugs belonging to the class of Aminoglycoside antibiotics.

Monitoring:

The monitoring of patients on Furosemide includes:

• Fluid status and creatinine must be monitored to prevent oliguria and azotemia.

• Monitoring potassium before and during rapid diuresis.

• The signs of ototoxicity must be observed at the higher dose.

• The doctors or physicians must maintain a chart for fluid intake and output.

• Vitals must also be monitored for orthostatic hypotension.

Toxicity:

Toxicity with Furosemide can occur as the extension of its diuretic activity. The main symptoms of overdose or toxicity with Furosemide include

• Blood volume reduction.

• Electrolyte imbalance.

• Dehydration.

• Hypochloremic alkalosis.

• Hypotension.

• Hypokalemia.

Treatment of overdose includes supportive measures, including replacing excessive fluid and electrolyte losses.

What Are the Interactions of Furosemide?

Drug interactions can result in decreased efficacy of the drug or can lead to adverse effects. The common interactions of Furosemide are as listed:

1. With Other Drugs:

• Aceclofenac.

• Acemetacin.

• Amikacin.

• Amikacin Liposome.

• Amtolmetin Guacil.

• Arsenic Trioxide.

• Aspirin.

• Bepridil.

• Bromfenac.

• Bufexamac.

• Celecoxib.

• Digitoxin.

• Dipyrone.

• Dofetilide.

• Droperidol.

• Fenoprofen.

• Fepradinol.

• Feprazone.

• Fexinidazole.

• Floctafenine.

• Flufenamic Acid.

• Gentamicin.

• Ibuprofen.

• Indomethacin.

• Kanamycin.

• Ketanserin.

• Ketoprofen.

• Ketorolac.

• Leflunomide.

• Levomethadyl.

• Lithium.

• Lornoxicam.

• Loxoprofen.

• Lumiracoxib.

• Meclofenamate.

• Mefenamic Acid.

• Meloxicam.

• Metolazone.

• Morniflumate.

• Nabumetone.

• Naproxen.

• Salsalate.

• Sodium Salicylate.

• Sotalol.

• Streptomycin.

• Sulindac.

• Tenoxicam.

• Teriflunomide.

• Tiaprofenic Acid.

• Tobramycin.

• Tolfenamic Acid.

• Tolmetin.

This list does not include all the interactions of Furosemide. Talk with the pharmacist to know more.

1. With Alcohol: Avoid using alcohol while taking Furosemide as it may worsen the side effects of Furosemide.

2. With Food: Avoid using diuretic herbs like juniper, hibiscus, buchu, and uva, as they can cause excessive urination. Avoid using licorice products as it may worsen the side effects.

Involvement of Healthcare Professionals:

The healthcare professional must carefully monitor the following in patients:

• Clinical condition.

• Fluid intake.

• Daily weight.

• Urine output.

• Electrolytes (potassium and magnesium).

• Kidney function (serum creatinine and serum blood urea nitrogen level).

Patients on Furosemide treatment in an ambulatory care setting must carefully monitor and evaluate their response to treatment. Further, intermittent electrolytes and kidney function monitoring are essential to replenish electrolytes and for managing the dose of Furosemide as indicated. Healthcare professionals must coordinate to help for positive patient results.