FDA Label for Lasix Onyu

1.1 Congestion

Lasix ONYU is indicated for the treatment of edema in adult patients with chronic heart failure.

2 Dosage And Administration

2.1 Dosage

The Infusor with single-dose prefilled cartridge delivers 30 mg of Lasix ONYU over the first hour followed by 12.5 mg per hour for the subsequent 4 hours [see Clinical Pharmacology (12)]. Administer Lasix ONYU once or twice daily as needed for edema. Lasix ONYU is not for chronic use and should be replaced with oral diuretics as soon as practical.

2.2 Important Administration Instructions

Lasix ONYU is intended for use in a setting where the patient can limit their activity for the duration of administration [see Warnings and Precautions (5.5)].

The Infusor for Lasix ONYU is not compatible with use in an MRI setting.

Inspect Lasix ONYU prefilled cartridge prior to administration. Lasix ONYU is a clear to slightly yellow solution. Do not use Lasix ONYU if solution is discolored or cloudy [see Description (11)] .

Refer to the Instructions for Use for additional information.

Push the Lasix ONYU prefilled cartridge into Disposable Unit. Slide the Reusable Unit and Disposable Unit together until the Status Light on the Reusable Unit turns on. The Infusor will remain ready to start infusion for 7 hours.

Peel away the paper liner on the 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. Make sure the Status Lights and the Start/Stop Button are facing up in a horizontal position.

Start the injection by firmly pressing and holding the Start/Stop Button until you hear the motor and see the blue Status Light change to flashing slowly.

Do not remove until the injection is complete which is signaled by the solid blue Status Light and the OK tone (one long beep).

Rotate the site of each subcutaneous administration.

3 Dosage Forms And Strengths

Injection: 80 mg per 2.67 mL as a clear to slightly yellow solution in a single-dose prefilled cartridge co-packaged with a single-use Disposable Unit of the Infusor.

4 Contraindications

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

5 Warnings And Precautions

5.1 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 possible vascular thrombosis and embolism, particularly in elderly patients. Serum electrolytes, CO₂, BUN, creatinine, glucose, and uric acid should be monitored frequently during furosemide therapy.

5.2 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 (12.3)].

5.3 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 (7)].

5.4 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.

5.5 Incomplete Dosing

The Lasix ONYU Infusor should not come in contact with water or any other fluids (blood or drug product). Fluid contact with the Infusor circuit board can lead to device errors and premature termination of infusion.
The Lasix ONYU 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.
Lasix ONYU should only be used in patients who can detect and respond to alarms to ensure a complete dose is administered.

6 Adverse Reactions

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

• Fluid, Electrolyte, and Metabolic Abnormalities [see Warnings and Precautions (5.1)].
• Ototoxicity [see Warnings and Precautions (5.3)]

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.

7 Drug Interactions

7.1 Effects Of Furosemide On Other Drugs

7.2 Effect Of Other Drugs On Furosemide

8 Use In Specific Populations

8.1 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 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 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.

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 rabbits 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.

8.2 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.

8.4 Pediatric Use

Safety and efficacy for pediatric use have not been established [see Indications and Usage (1)].

8.5 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.

Lasix ONYU 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 (12.3)].

8.6 Renal Impairment

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

8.7 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.

10 Overdosage

The principal signs and symptoms of overdose with Lasix ONYU 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.

11 Description

Lasix ONYU (furosemide injection) for subcutaneous use is a loop diuretic. Chemically, it is 4-chloro-N-furfuryl-5-sulfamoylanthranilic 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:

image-Structure - structure

Molecular Formula: C₁₂H₁₁ClN₂O₅S

Molecular Weight: 330.75 g/mol

Lasix ONYU is a single-dose prefilled cartridge co-packaged with a single-use Disposable Unit of the Infusor.

The single-dose prefilled cartridge contains 80 mg furosemide in a 2.67 mL sterile, clear to slightly yellow, and nonpyrogenic aqueous solution. The pH of Lasix ONYU, 7.5, differs from that of Furosemide Injection, USP. Each 1 mL dose of Lasix ONYU contains 30 mg of furosemide and the following inactive ingredients: betadex sulfobutyl ether sodium (300 mg), hydrochloric acid for pH adjustment if needed, sodium hydroxide for pH adjustment if needed, tromethamine (3 mg), and water for injection (q.s.).

Each single-dose of Lasix ONYU is administered via an electromechanical (battery powered, microprocessor controlled) Infusor, pre-programmed to deliver 80 mg of Lasix ONYU over 5-hours using a bi-phasic delivery profile. The Infusor consists of a custom Reusable Unit which can be used for close to 50 treatments. The Reusable Unit is used with a Disposable Unit and single-dose prefilled cartridge which are provided together for the user as a Lasix ONYU Kit. The Disposable Unit must be discarded after use.

12.1 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.

12.2 Pharmacodynamics

In patients with NYHA Class II and Class III heart failure, subcutaneous administration of Lasix ONYU (30 mg furosemide over the first hour followed by 12.5 mg per hour for the subsequent 4 hours, total 80 mg furosemide within 5 hours) produced similar diuresis and natriuresis to intravenous administration (single 80 mg bolus) at 8- and 24-hour post-dose. The duration of diuretic effect with Lasix ONYU is at least 8 hours after initiation of dosing.

12.3 Pharmacokinetics

Absorption

In patients with NYHA Class II and Class III heart failure, subcutaneous infusion of Lasix ONYU (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 112% (90% CI: 104, 120%), with a median Tmax of 5 hours relative to 80 mg intravenous furosemide (single 80 mg bolus). The pharmacokinetic parameters of Lasix ONYU are presented in Table 3 below:

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

The impact of subcutaneous edema at the administration site of Lasix ONYU 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.

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).

Metabolism

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

13.1 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.

16 How Supplied/Storage And Handling

Lasix ONYU injection is a sterile, clear to slightly yellow, non-pyrogenic liquid supplied in a single-dose prefilled cartridge for subcutaneous infusion co-packaged with a Disposable Unit. The Infusor with single-dose prefilled cartridge is designed to deliver 80 mg of Lasix ONYU in 2.67 mL solution over 5 hours.

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 Lasix ONYU from light. Do not remove the prefilled cartridge from carton until it is ready for use. Do not use if the solution is discolored or cloudy. Protect the Infusor from water.

17 Patient Counseling Information

Advise the patient and/or caregiver to read the FDA-approved patient labeling [Instructions for Use].

Advise the patient that Lasix ONYU should not 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 (5.5)].

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 (5.1)].

Advise patients that furosemide may increase blood glucose levels and thereby affect urine glucose tests [see Warnings and Precautions (5.1)].

Photosensitivity

The skin of some patients may be more sensitive to the effects of sunlight while taking furosemide [see Adverse Reactions (6)].

For more information about Lasix® ONYU, go to www.Lasix-ONYU.com or call 1-855-452-7496 (1-855-4LASIX6).

image-logo - logo

Lasix^® ONYU (furosemide injection 80 mg/2.67 mL) for subcutaneous use

Manufactured for:
SQ Innovation, Inc.
20 Burlington Mall Road, Suite 220
Burlington, MA 01803
USA

Patent Protected
©2023

Sq Innovationinstructions For Uselasix® Onyu (Lay-Six On-Yoo) (Furosemide Injection) 80 Mg/2.67 Ml (30 Mg/Ml) For Subcutaneous Use With Infusor

These Instructions for Use contains information on how to use Lasix ONYU with the Infusor.

image-3 - image 3 infusor blue status blue tab

Contact Information:
SQ Innovation, Inc.
Burlington, MA 01803, USA
Phone: 1-855-452-7496 (1-855-4LASIX6)
www.Lasix-ONYU.com

1: Important Information You Need to Know 

Before Using the Lasix ONYU Infusor

• Keep the Lasix ONYU Infusor out of sight and reach of children.
• The Lasix ONYU treatment is for adult patients only as prescribed by a healthcare provider.
• For subcutaneous (under the skin) use only. The Lasix ONYU Infusor delivers the medicine just under the skin.
• Use on the stomach only. Do not use on any other area of the body.
• The Lasix ONYU Infusor is intended to be used by a single person and should not be shared.
• Do not use the Prefilled Cartridge if the solution is cloudy, yellow-brown or contains floating particles. It should be clear or light yellow. If it is not clear or light yellow, contact your healthcare provider to get a new one.
• Do not use any part of the Lasix ONYU Infusor if it has expired. If it is expired, contact your healthcare provider to get a new one.
• Do not use any part of the Lasix ONYU Infusor (Prefilled Cartridge, Disposable Unit, Reusable Unit or Charger) if it appears to be broken or damaged or does not work right. Use a new one or call SQ Innovation at 1-855-452-7496.
• Do not use a Disposable Unit if it was dropped as it may be damaged or contaminated. Use a new one.
• Do not use the Lasix ONYU Infusor if you can see the needle. Do not touch the needle or put the Lasix ONYU Infusor on your stomach, as you may get an injury. Go to Troubleshooting: You Can See the Needle for instructions on what to do.
• Do not use more than 1 Lasix ONYU Infusor at a time.
• Do not do more than 2 infusions in a 24-hour period.
• Do not use a Disposable Unit or Prefilled Cartridge more than 1 time.

Before Starting a Treatment

• Talk with your healthcare provider before using the Lasix ONYU Infusor.
  Do not start an infusion unless directed to do so by your healthcare provider.
• A healthcare provider should train you before using the Lasix ONYU Infusor by yourself.
• Read the step-by-step instructions (go to Chapter 2: How to Use the Lasix ONYU Infusor) before using the Lasix ONYU Infusor by yourself.
• You may watch the optional training video.

During a Treatment

• Start the infusion within 7 hours of preparing the Lasix ONYU Infusor.
• The infusion will last about 5 hours. During this time, you should limit your activities so that your bending movements are limited. Wearing the Lasix ONYU Infusor while riding in a car or airplane is not recommended. Be sure you have access to a bathroom after starting the infusion. You should urinate (pee) a lot and will need to make frequent bathroom visits.
• Frequent urination is to be expected during use of the Lasix ONYU Infusor. Be sure you have access to a bathroom for up to 8 hours after starting the infusion.
• Call your healthcare provider if you did not urinate a lot (at least 2 times during the 5-hour infusion).
• Do not apply lotions, oils, or ointments to the stomach area where you will apply the Lasix ONYU Infusor.
• Do not get the Lasix ONYU Infusor wet. Doing so may damage the Lasix ONYU Infusor. Do not shower, bathe, or swim while wearing the Lasix ONYU Infusor.
• Do not remove the Lasix ONYU Infusor from the stomach until the infusion is done. Removing the Lasix ONYU Infusor before stopping it will expose the needle, and may injure you or others. Go to How to Stop the Lasix ONYU Infusor Early if you need to stop the infusion early.
• Do not use the Lasix ONYU Infusor in or around a Magnetic Resonance Imaging (MRI) machine.
• Do not use the Lasix ONYU Infusor within 12 inches of mobile phones, tablets, computers, or wireless accessories (for example: TV remote control, Bluetooth computer keyboard or mouse) during the 5-hour infusion. It may cause the Lasix ONYU Infusor to break.