REGIOCIT

REGIOCIT- sodium chloride and sodium citrate, unspecified form injection, solution
Baxter Healthcare Corporation

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Emergency Use Authorization (EUA) for REGIOCIT (Sodium Chloride and Sodium Citrate Renal Replacement and Regional Anticoagulant Solution)

FACT SHEET FOR HEALTHCARE PROVIDERS

REGIOCIT

(Sodium Chloride and Sodium Citrate Renal Replacement and Regional Anticoagulant solution) For continuous renal replacement therapy

For extracorporeal use only

Emergency Use Authorization for the United States

The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to permit the emergency use of the unapproved product, REGIOCIT: a replacement solution that contains citrate for Regional Citrate Anticoagulation (RCA) of the extracorporeal circuit. REGIOCIT has been authorized for emergency use as a replacement solution in adult patients treated with Continuous Renal Replacement Therapy (CRRT), and for whom RCA is appropriate, during the COVID-19 pandemic. REGIOCIT is intended for use in a critical care setting. REGIOCIT is intended to be used in continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF) modalities. Use of REGIOCIT is limited to healthcare providers and/or institutions that Baxter has qualified to administer REGIOCIT for these emergency uses.

REGIOCIT has been authorized by FDA for emergency use. REGIOCIT is not FDA-approved.

REGIOCIT is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of REGIOCIT under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

The scope of the EUA is as follows:

•

REGIOCIT will be used as a replacement solution only in adult patients being treated with CRRT and for whom RCA is appropriate.

•

REGIOCIT will be administered only by a licensed healthcare provider in a critical care setting.

•

REGIOCIT will available for use only in facilities that Baxter Healthcare Corporation has qualified and provided appropriate training on the use of REGIOCIT.

Product Description

REGIOCIT is a sterile, replacement solution intended for use in adult patients being treated with CRRT and for whom RCA is appropriate. REGIOCIT, contains physiological concentrations of sodium (140 mmol/l), chloride (86 mmol/l), and a low concentration of citrate (18 mmol/L).

IMPORTANT ADMINISTRATION INSTRUCTIONS: • A separate systemic infusion of calcium must be administered during use of REGIOCIT to prevent or treat hypocalcemia. Blood calcium concentrations (ionized and total) must be monitored throughout CRRT. • REGIOCIT solution must be used in pre-dilution mode only, with appropriate extracorporeal renal replacement equipment intended for CRRT, using an integrated pre-blood pump for RCA and in combination with other replacement and/or dialysate solution to provide the recommended dose of CRRT. • REGIOCIT may only be administered by health care providers/institutions that have been qualified by Baxter to administer the product.

Instructions for Use

DOSAGE AND ADMINISTRATION

1.1 Administration Instructions

Renal Replacement Solution: Not for direct intravenous infusion.

The recommended effluent volume for patients receiving CRRT for acute kidney injury (AKI) is 20 to 25 mL/kg/h. This usually requires a higher prescription of effluent volume. The prescription of REGIOCIT solution must consider the flow rates of the effluent and other therapeutic fluids, the patient’s fluid removal requirements, additional fluid inputs and outputs, and the desired acid-base and electrolyte balance.

The mode of therapy, solute formulations, flow rates and length of therapy should be selected by the physician responsible for managing treatment depending on the clinical condition of the patient as well as the patient’s fluid, electrolyte, acid base and glucose balance.

Dialysate and replacement fluid formulations and flow rates are prescribed in accordance with the patient’s clinical needs. The use of a calcium-containing dialysate or replacement fluid is not recommended, since the calcium provided by these solutions may counteract the anticoagulant effect of citrate in the circuit.

1.2 Suggested Dosing

The rate at which REGIOCIT solution is administered depends on the targeted citrate dose and the prescribed blood flow rate. The pre-filter infusion rate of REGIOCIT solution is indexed to the blood flow rate to achieve a target blood citrate concentration of 3 mmol/L of blood (See Table 1). Flow rate for anticoagulation of the extracorporeal circuit should be titrated to achieve a post-filter concentration of ionized calcium in the range of 0.25 to 0.35 mmol/L.

Table 1: REGIOCIT Solution Flow Rates to Achieve Citrate Dose of 3 mmol/L of Blood

Prior to initiating therapy, the patient’s systemic ionized calcium concentration should be within the normal physiologic range (1.0 to 1.2 mmol/L) by adjustment of calcium supplementation. A separate infusion of calcium is always required during use of REGIOCIT, due to loss in the effluent. Calcium solution infusion is commenced at the rate of 4 mmol/h, when commencing therapy (see Table 4). Adjust or stop calcium infusion according to physician’s prescription when REGIOCIT is stopped.

Citrate also acts as a buffer source (due to conversion to bicarbonate); the infusion rate of REGIOCIT solution must be considered in relation to the rate at which buffer administration occurs from other sources (e.g., dialysate and/or replacement fluid). REGIOCIT solution must be used together with a dialysis solution/replacement solution with appropriate bicarbonate concentration.

1.3 Laboratory Monitoring

Monitoring of the post-filter blood ionized calcium (iCa), systemic blood iCa, and total blood calcium levels in conjunction with other laboratory and clinical parameters such as acid-base balance and serum electrolytes are essential to guide appropriate REGIOCIT solution dosage based on the desired level of anticoagulation. Levels should be taken at baseline, 1 hour after initiation (or adjustment), and every 6 hours (See Table 2). Rapidly decreasing systemic ionized calcium levels are an early indicator of citrate accumulation.

Measurement of total calcium and assessment of total-to-ionized calcium ratio is necessary. Citrate accumulation causes systemic ionized calcium levels to drop and the ratio of total-to-ionized calcium increases (total-to-ionized calcium ratio > 2.5). In the presence of impaired citrate metabolism, a progressively higher calcium infusion rate is required to maintain the systemic ionized calcium concentration within the intended target. When a total-to-ionized-calcium ratio > 2.5 is recorded, any one of the following abnormalities reported concurrently increases the likelihood of citrate accumulation:

o

A rapid decline in systemic iCa concentration despite adequate calcium compensation

o

A rapid decrease in pH or a decrease in base excess

o

A rapid increase in anion gap

In order to avoid metabolic alkalosis, acid-base balance and systemic ionized calcium can be measured using blood gas analysis. If metabolic alkalosis or citrate accumulation is suspected, decrease the citrate dose while tolerating a post-filter ionized calcium of < 0.5 mmol/L. This can be achieved by either decreasing the blood flow rate to decrease the overall citrate load, increasing the dialysate/replacement flow rate (when applicable) to increase the citrate removal, or decreasing the citrate flow to decrease the citrate dose. Dialysate solutions contain bicarbonate below or above physiological range of 22 to 26 mmol/L, and increasing or decreasing the flow rates of the dialysate solutions can impact the acid-base status of the patient.

Plasma levels of sodium, magnesium, potassium, and glucose, and phosphate should be monitored regularly and should be supplemented as needed.

Table 2 provides a summary of the most important parameters to be monitored during RCA therapy, as well as options for adjustment.

Table 2: Monitoring and Adjustment During RCA Therapy

Table 3 provides the REGIOCIT solution flow rate adjustment based on a citrate dose adjustment of 0.5 mmol/L.

Table 3: REGIOCIT Solution Flowrate Adjustment Based on a Citrate Dose Adjustment of 0.5 mmol/L

Table 4 provides recommendations to maintain a systemic ionized calcium level between 1.0 mmol/L and 1.2 mmol/L.

Table 4: Sliding Scale of Calcium Infusion