Furoscix

Description for Furoscix

FUROSCIX (furosemide injection 80 mg/10 mL) is a loop diuretic which is an anthranilic acid derivative.

Chemically, it is 4chloroNfurfuryl5sulfamoylanthranilic acid.

Furosemide is a white to slightly yellow crystalline powder. It is sparingly soluble in alcohol, freely soluble in dilute alkali solutions and insoluble in dilute acids. The structural formula is as follows:

FUROSCIX is a single-dose prefilled cartridge co-packaged with a single-use, on-body infusor. The single-dose prefilled cartridge contains 80 mg per 10 mL sterile, clear to slightly yellow, and nonpyrogenic furosemide solution. The pH of FUROSCIX, 7.4, differs from that of Furosemide Injection, USP.

Each 1 mL of FUROSCIX contains the following inactive ingredients: hydrochloric acid for pH adjustment if needed, sodium chloride (5.84 mg), sodium hydroxide for pH adjustment if needed, tris HCl (7.88 mg), and water for injection (q.s.).

FUROSCIX is administered via a wearable, single-use, electromechanical (battery powered, microprocessor controlled), on-body delivery system that is pre-programmed to deliver 80 mg of FUROSCIX over 5-hours using a bi-phasic delivery profile.

Uses for Furoscix

FUROSCIX is indicated for the treatment of edema in adult patients with chronic heart failure or chronic kidney disease (CKD), including the nephrotic syndrome.

Dosage for Furoscix

Dosage

The single-use, On-body Infusor with prefilled cartridge is pre-programmed to deliver 30 mg of furosemide over the first hour followed by 12.5 mg per hour for the subsequent 4 hours [see Use In Specific Populations and CLINICAL PHARMACOLOGY].

FUROSCIX is not for chronic use and should be replaced with oral diuretics as soon as practical.

Important Administration Instructions

FUROSCIX is intended for use in a setting where the patient can limit their activity for the duration of administration [see WARNINGS AND PRECAUTIONS].

FUROSCIX is not compatible with use in an MRI setting. Inspect FUROSCIX prefilled cartridge prior to administration. FUROSCIX is a clear to slightly yellow solution. Do not use FUROSCIX if solution is discolored or cloudy [see DESCRIPTION].

Refer to the Instructions for Use for additional information.

Load the prefilled cartridge of furosemide into the On-body Infusor and close the cartridge holder.

Peel away the adhesive liner on the On-body Infusor and apply onto a clean, dry area of the abdomen between the top of the beltline and the bottom of the ribcage that is not tender, bruised, red or indurated. The distance from the top of the beltline to the bottom of the ribcage should be at least 2 ½ inches.

Start the injection by firmly pressing and releasing the blue start button.

Do not remove until the injection is complete (signaled by the solid green status light, beeping sound, and the white plunger rod filling the cartridge window).

Rotate the site of each subcutaneous administration.

HOW SUPPLIED

Dosage Forms And Strengths

Injection: 80 mg/10 mL (8 mg/mL) as a clear to slightly yellow solution in a single-dose prefilled cartridge for use only with co-packaged single-use, On-body Infusor.

Storage And Handling

FUROSCIX injection is a sterile, clear to slightly yellow, non-pyrogenic liquid supplied in a single-dose prefilled cartridge for subcutaneous infusion co-packaged with the On-body Infusor. Each single-use On-body Infusor with prefilled cartridge is designed to deliver 80 mg of FUROSCIX in 10 mL solution over 5-hours.

Carton containing one 80 mg/10 mL (8 mg/mL) prefilled cartridge co-packaged with one On-body Infusor

NDC 71767-100-01

Store between 20°C and 25°C (68°F and 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP Controlled Room Temperature]. Do not refrigerate or freeze.

Protect FUROSCIX from light. Do not remove the cartridge from carton until it is ready for use. Do not use if the solution is discolored or cloudy. Protect the On-body Infusor from water.

Manufactured for: scPharmaceuticals, Inc., 25 Mall Road, Suite 203, Burlington, MA 01803. Revised: Mar 2025

Side Effects for Furoscix

The following important adverse reactions are discussed elsewhere in the labeling:

• Fluid, Electrolyte, and Metabolic Abnormalities [see WARNINGS AND PRECAUTIONS].
• Ototoxicity [see WARNINGS AND PRECAUTIONS]

The following adverse reactions associated with the use of furosemide were identified in clinical trials or post-marketing reports. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably, or to establish a causal relationship to drug exposure.

Adverse reactions are categorized below by organ system and listed by decreasing severity.

Gastrointestinal System Reactions: pancreatitis, jaundice (intrahepatic cholestatic jaundice), increased liver enzymes, anorexia, oral and gastric irritation, cramping, diarrhea, constipation, nausea, vomiting.

Systemic Hypersensitivity Reactions: severe anaphylactic or anaphylactoid reactions (e.g., with shock), systemic vasculitis, interstitial nephritis, necrotizing angiitis.

Central Nervous System Reactions: tinnitus and hearing loss, paresthesias, vertigo, dizziness, headache, blurred vision, xanthopsia.

Hematologic Reactions: aplastic anemia, thrombocytopenia, agranulocytosis, hemolytic anemia, leukopenia, anemia, eosinophilia.

Dermatologic Hypersensitivity Reactions: toxic epidermal necrolysis, Stevens-Johnson Syndrome, erythema multiforme, drug rash with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, exfoliative dermatitis, bullous pemphigoid, purpura, photosensitivity, rash.

Cardiovascular Reactions: orthostatic hypotension, increase in cholesterol and triglyceride serum levels.

Administration Site and Skin Reactions: erythema, bruising, edema, infusion site pain.

Other Reactions: glycosuria, muscle spasm, weakness, restlessness, urinary bladder spasm, thrombophlebitis, transient injection site pain following intramuscular injection, fever.

Drug Interactions for Furoscix

Effects Of Furosemide On Other Drugs

Drug/Substance Class or Name	Drug Interaction Effect	Recommendations
Aminoglycoside antibiotics	Furosemide may increase the ototoxic potential of aminoglycoside antibiotics, especially in the presence of impaired renal function [see WARNINGS AND PRECAUTIONS ].	Avoid combination except in life threatening situations.
Ethacrynic acid	Possibility of ototoxicity [see WARNINGS AND PRECAUTIONS ].	Avoid concomitant use with ethacrynic acid.
Salicylates	May experience salicylate toxicity at lower doses because of competitive renal excretory sites.	Monitor for symptoms of salicylate toxicity.
Cisplatin	There is a risk of ototoxic effects if cisplatin and furosemide are given concomitantly [see WARNINGS AND PRECAUTIONS].
Cisplatin and nephrotoxic drugs	Nephrotoxicity	Administer furosemide at lower doses and with positive fluid balance when used to achieve forced diuresis during cisplatin treatment. Monitor renal function.
Paralytic agents	Furosemide has a tendency to antagonize the skeletal muscle relaxing effect of tubocurarine and may potentiate the action of succinylcholine.	Monitor for skeletal muscle effect.
Lithium	Furosemide reduces lithium’s renal clearance and add a high-risk of lithium toxicity.	Avoid concomitant use with lithium.
Angiotensin converting enzyme inhibitors or angiotensin II receptor blockers	May lead to severe hypotension and deterioration in renal function, including renal failure.	Monitor for changes in blood pressure and renal function and interrupt or reduce the dosage of furosemide, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers if needed.
Antihypertensive drugs	Furosemide may add to or potentiate the therapeutic effect of other antihypertensive drugs.	Monitor for changes in blood pressure and adjust the dose of other antihypertensive drugs if needed.
Adrenergic blocking drugs or peripheral adrenergic blocking drugs	Potentiation occurs.	Monitor for changes in blood pressure and adjust the dose of adrenergic blocking drugs if needed.
Norepinephrine	Furosemide may decrease arterial responsiveness (vasoconstricting effect) to norepinephrine.	Monitor blood pressure (or mean arterial pressure).
Chloral hydrate	In isolated cases, intravenous administration of furosemide within 24 hours of taking chloral hydrate may lead to flushing, sweating attacks, restlessness, nausea, increase in blood pressure, and tachycardia.	Concomitant use with chloral hydrate is not recommended.
Methotrexate and other drugs undergoing renal tubular secretion	Furosemide may decrease renal elimination of other drugs that undergo tubular secretion. High-dose treatment of furosemide may result in elevated serum levels of these drugs and may potentiate their toxicity.	Monitor serum levels of drugs undergoing renal tubular secretion and adjust the dose if needed.
Cephalosporin	Furosemide can increase the risk of cephalosporin-induced nephrotoxicity even in the setting of minor or transient renal impairment.	Monitor for changes in renal function.
Cyclosporine	Increased risk of gouty arthritis secondary to furosemide-induced hyperuricemia and cyclosporine impairment of renal urate excretion.	Monitor serum urate levels.
Thyroid hormones	High-doses (> 80 mg) of furosemide may inhibit the binding of thyroid hormones to carrier proteins and result in transient increase in free thyroid hormones, followed by an overall decrease in total thyroid hormone levels.	Monitor the total thyroid hormone levels

Effect Of Other Drugs On Furosemide

Drug/Substance Class or Name	Drug Interaction Effect	Recommendations
Phenytoin	Phenytoin interferes directly with renal action of furosemide.	Monitor diuretic effects of furosemide and adjust the dose of furosemide if needed.
Methotrexate and other drugs undergoing renal tubular secretion	May reduce the effect of furosemide. High-dose treatment of methotrexate and these other drugs may result in elevated serum levels of furosemide and may potentiate the toxicity of furosemide.	Monitor for enhanced toxicity of furosemide.
Indomethacin	Coadministration of indomethacin may reduce the natriuretic and antihypertensive effects of furosemide in some patients by inhibiting prostaglandin synthesis. Indomethacin may also affect plasma renin levels, aldosterone excretion, and renin profile evaluation.	Patients receiving both indomethacin and furosemide should be observed closely to determine if the desired diuretic and/or antihypertensive effect of furosemide is achieved.

Warnings for Furoscix

Included as part of the "PRECAUTIONS" Section

Precautions for Furoscix

Fluid, Electrolyte, And Metabolic Abnormalities

Furosemide may cause fluid, electrolyte, and metabolic abnormalities such as hypovolemia, hypokalemia, azotemia, hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypocalcemia, hyperglycemia, or hyperuricemia, particularly in patients receiving higher doses, patients with inadequate oral electrolyte intake, and in elderly patients. Excessive diuresis may cause dehydration and blood volume reduction with circulatory collapse and possibly vascular thrombosis and embolism, particularly in elderly patients. Serum electrolytes, CO2, BUN, creatinine, glucose, and uric acid should be monitored frequently during furosemide therapy [see Use In Specific Populations].

Worsening Renal Function

Furosemide can cause dehydration and azotemia. If increasing azotemia and oliguria occur during treatment of severe progressive renal disease, discontinue furosemide [see CLINICAL PHARMACOLOGY].

Ototoxicity

Cases of tinnitus and reversible or irreversible hearing impairment and deafness have been reported with furosemide. Reports usually indicate that furosemide ototoxicity is associated with rapid injection, severe renal impairment, the use of higher than recommended doses, hypoproteinemia or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. If the physician elects to use high-dose parenteral therapy, controlled intravenous infusion is advisable (for adults, an infusion rate not exceeding 4 mg furosemide per minute has been used) [see DRUG INTERACTIONS].

Acute Urinary Retention

In patients with severe symptoms of urinary retention (because of bladder emptying disorders, prostatic hyperplasia, urethral narrowing), the administration of furosemide can cause acute urinary retention related to increased production and retention of urine. These patients require careful monitoring, especially during the initial stages of treatment.

Incomplete Dosing

The On-body Infusor should not be allowed to get wet from water or any other fluids (blood or drug product). Fluid contact with the circuit board can lead to device errors and premature termination of infusion.

The On-body Infusor is intended for use in a setting where the patient can limit their activity for the duration of administration. Certain patient movements may cause interruption of device adherence to skin and premature termination of infusion.

The On-body Infusor for FUROSCIX should only be used in patients who can detect and respond to alarms to ensure a complete dose is administered.

Patient Counseling Information

Advise the patient and/or caregiver to read the FDA-approved patient labeling [see FDA-approved INSTRUCTIONS FOR USE].

Advise the patient that they should not allow the On-body Infusor to come into contact with water or other fluids. Patients should check the device for alarms to ensure a complete dose is administered [see WARNINGS AND PRECAUTIONS].

Fluid, Electrolyte, And Metabolic Abnormalities

Advise patients that they may experience symptoms from excessive fluid and/or electrolyte losses. The postural hypotension that sometimes occurs can usually be managed by getting up slowly. Potassium supplements and/or dietary measures may be needed to control or avoid hypokalemia [see WARNINGS AND PRECAUTIONS].

Advise patients that furosemide may increase blood glucose levels and thereby affect urine glucose tests [see WARNINGS AND PRECAUTIONS].

Photosensitivity

The skin of some patients may be more sensitive to the effects of sunlight while taking furosemide [see ADVERSE REACTIONS].

Advise hypertensive patients to avoid medications that may increase blood pressure, including over-thecounter products for appetite suppression and cold symptoms [see DRUG INTERACTIONS].

For more information about FUROSCIX, go to www.FUROSCIX.com or call 1-855-SCPHARMA (1-855-727-4276)

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

Furosemide was tested for carcinogenicity by oral administration in one strain of mice and one strain of rats. A small but significantly increased incidence of mammary gland carcinomas occurred in female mice at a dose approximately 8 times a human i.v. dose of 80 mg based on BSA and oral bioavailability corrections. There were marginal increases in uncommon tumors in male rats at a dose of 15 mg per kg (slightly greater than the maximum human dose) but not at 30 mg per kg.

Mutagenesis

Furosemide was devoid of mutagenic activity in various strains of Salmonella typhimurium when tested in the presence or absence of an in vitro metabolic activation system, and questionably positive for gene mutation in mouse lymphoma cells in the presence of rat liver S9 at the highest dose tested. Furosemide did not induce sister chromatid exchange in human cells in vitro, but other studies on chromosomal aberrations in human cells in vitro gave conflicting results. In Chinese hamster cells it induced chromosomal damage but was questionably positive for sister chromatid exchange. Studies on the induction by furosemide of chromosomal aberrations in mice were inconclusive. The urine of rats treated with this drug did not induce gene conversion in Saccharomyces cerevisiae.

Impairment Of Fertility

Furosemide produced no impairment of fertility in male or female rats, at 100 mg per kg per day (the maximum effective diuretic dose in the rat), approximately 7 times a human i.v. dose of 80 mg based on BSA and oral bioavailability corrections.

Use In Specific Populations

Pregnancy

Risk Summary

Available data from published observational studies, case reports, and post marketing reports, from decades of use, have not demonstrated a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes with furosemide use during pregnancy. Untreated congestive heart failure and cirrhosis of the liver can lead to adverse outcomes for the mother and the fetus (see Clinical Considerations).

In animal reproduction studies, furosemide has been shown to cause unexplained maternal deaths and abortions in rabbits when administered orally during organogenesis at 4 times a human i.v. dose of 80 mg based on body surface area (BSA) and oral bioavailability corrections, presumably secondary to volume depletion (see Data).

The estimated background risk for major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-associated Maternal and/or Embryo/fetal Risk

Pregnant women with congestive heart failure are at increased risk for pre-term birth. Stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester. Clinical classification of heart disease may worsen with pregnancy and lead to maternal death and/or stillbirth. Closely monitor pregnant patients for destabilization of their heart failure.

Pregnant women with symptomatic cirrhosis generally have poor outcomes including hepatic failure, variceal hemorrhage, pre-term delivery, fetal growth restriction and maternal death. Outcomes are worse with coexisting esophageal varices. Carefully monitor pregnant women with cirrhosis of the liver.

Data

Animal Data

The effects of furosemide on embryonic and fetal development and on pregnant dams were studied in mice, rats, and rabbits.

Furosemide caused unexplained maternal deaths and abortions in the rabbit at the lowest dose of 25 mg/kg (approximately 4 times the human i.v. dose of 80 mg based on BSA and oral bioavailability corrections). In another study, a dose of 50 mg/kg (approximately 7 times a human i.v. dose of 80 mg based on BSA and oral bioavailability corrections) also caused maternal deaths and abortions when administered to rabbits between Days 12 and 17 of gestation. In a third study, none of the pregnant rabbits survived an oral dose of 100 mg/kg. Data from the above studies indicate fetal lethality that can precede maternal deaths.

The results of the mouse study and one of the three rabbit studies also showed an increased incidence and severity of hydronephrosis (distention of the renal pelvis and, in some cases, of the ureters) in fetuses of treated dams as compared with the incidence of fetuses from the control group.

Lactation

Risk Summary

The presence of furosemide has been reported in human breast milk. There are no data on the effects on the breastfed infant or the effects on milk production. Doses of furosemide associated with clinically significant diuresis may impair milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for furosemide and any potential adverse effects on the breastfed infant from furosemide or from the underlying maternal condition.

Pediatric Use

Safety and efficacy for pediatric use have not been established [see INDICATIONS AND USAGE].

Geriatric Use

Controlled clinical studies did not include sufficient numbers of subjects to determine whether subjects aged 65 and over respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for the elderly patients should be cautious, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

FUROSCIX is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see CLINICAL PHARMACOLOGY].

Renal Impairment

Significantly reduced renal function can affect the response to furosemide. The On-body Infusor will deliver only an 80 mg dose of furosemide, and patients with significantly reduced renal function may require additional diuretic therapy.

Hepatic Impairment

In patients with hepatic cirrhosis and ascites, sudden alterations of fluid and electrolyte balance may precipitate hepatic encephalopathy and coma. Treat such patients in a setting where clinical status and electrolyte balance can be carefully monitored.

Overdose Information for Furoscix

The principal signs and symptoms of overdose with FUROSCIX are dehydration, blood volume reduction, hypotension, electrolyte imbalance, hypokalemia and hypochloremic alkalosis, and are extensions of its diuretic action.

The concentration of furosemide in biological fluids associated with toxicity or death is not known.

Treatment of overdosage is supportive and consists of replacement of excessive fluid and electrolyte losses. Serum electrolytes, carbon dioxide level and blood pressure should be determined frequently. Adequate drainage must be assured in patients with urinary bladder outlet obstruction (such as prostatic hypertrophy).

Hemodialysis does not accelerate furosemide elimination.

Contraindications for Furoscix

• FUROSCIX is contraindicated in patients with anuria.
• FUROSCIX is contraindicated in patients with a history of hypersensitivity to furosemide, any component of the FUROSCIX formulation, or medical adhesives.

Clinical Pharmacology for Furoscix

Mechanism Of Action

Furosemide primarily inhibits the reabsorption of sodium and chloride in the proximal and distal tubules and in the loop of Henle. The high degree of diuresis is largely due to the unique site of action. The action on the distal tubule is independent of any inhibitory effect on carbonic anhydrase and aldosterone.

Pharmacodynamics

In patients with NYHA Class II and Class III heart failure, subcutaneous administration of FUROSCIX (30 mg furosemide over the first hour followed by 12.5 mg per hour for the subsequent 4 hours, total 80 mg furosemide) produced similar diuresis and natriuresis to intravenous administration (two 40 mg bolus doses separated by 120 minutes) at 8 and 24 hour post-dose. The duration of diuretic effect with FUROSCIX is up to 8 hours after initiation of dosing.

Pharmacokinetics

Absorption

In patients with NYHA Class II-III congestive heart failure, subcutaneous infusion of FUROSCIX (30 mg furosemide over the first hour followed by 12.5 mg per hour for the subsequent 4 hours, 80 mg furosemide total), the bioavailability was 99.6% (90% CI: 94.8, 104.8) with a median Tmax of 4 hours relative to 80 mg intravenous furosemide (two 40-mg bolus doses separated by 120 minutes). The pharmacokinetic parameters of FUROSCIX are presented in Table 1 below:

Table 1: Pharmacokinetic Data of FUROSCIX Following Subcutaneous Infusion (n = 15)

Dose	Cmax (ng/mL)	AUCt (ng×hr/mL)	T1/2 (hr)	AUC∞ (ng×hr/mL)
FUROSCIX: 30 mg subcutaneously infused over the first hour followed by 12.5 mg per hour for the subsequent 4 hours (total dose: 80 mg furosemide)	2040 ± 449	13000 ± 4000	3.2 ± 0.9	13100 ± 4010
Furosemide administered as 2 x 40 mg bolus doses intravenously, separated by 120 minutes (total dose: 80 mg furosemide)	8580 ± 2540	13000 ± 4050	2.6 ± 0.3	13200 ± 4170

The terminal half-life of furosemide is approximately 2 hours.

The impact of subcutaneous edema at the administration site of FUROSCIX on drug absorption is unknown.

Distribution

Furosemide is extensively bound to plasma proteins, mainly to albumin. Plasma concentrations ranging from 1 mcg per mL to 400 mcg per mL are 91% to 99% bound in healthy individuals. The unbound fraction averages 2.3% to 4.1% at therapeutic concentrations.

Furosemide binding to albumin may be reduced in elderly patients.

Metabolism

Furosemide glucuronide is the only or at least the major biotransformation product of furosemide in man.

Elimination

Significantly more furosemide is excreted in urine following the intravenous injection than after the tablet or oral solution.

Furosemide is predominantly excreted unchanged in the urine.

The renal clearance of furosemide after intravenous administration in older healthy male subjects (60 to 70 years of age) is significantly less than in younger healthy male subjects (20 to 35 years of age).

Patient Information for Furoscix

No information provided. Please refer to the WARNINGS AND PRECAUTIONS section.