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Anticoagulant citrate dextrose: Drug information

Anticoagulant citrate dextrose: Drug information
For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • ACD Formula A;
  • ACD-A noClot-50
Pharmacologic Category
  • Anticoagulant
Dosing: Adult
Regional anticoagulation for continuous renal replacement therapy circuit

Regional anticoagulation for continuous renal replacement therapy circuit (off-label use): Note: Citrate solution must only be prescribed and administered by trained personnel, as standardized (and often specialized) dialysate and/or replacement fluids and titration and monitoring protocols are required (Ref). Citrate solution is administered through the inflow (prefilter or “arterial”) limb of the extracorporeal CRRT circuit, not administered directly to the patient (Ref). Safety: Use is generally considered contraindicated in patients likely to have impaired citrate clearance (eg, acute liver failure with transaminases >1,000 units/L); however, if necessary, may be used with close monitoring and appropriate adjustments (Ref). When regional citrate anticoagulation is utilized, calcium is lost in the dialysis effluent in the form of citrate-calcium complexes. Calcium repletion must be administered to avoid hypocalcemia. Calcium may be infused at the end of the dialysis circuit or IV through a separate central line (Ref).

Example regimen:

Initial infusion rate ( in mL/hour ): Intracircuit: Use ACD-A solution: Approximate usual initial infusion rate: ~1.5 to 1.8 times the blood flow rate; for example, if blood flow rate is 100 to 200 mL/minute, start ACD-A infusion at 150 to 360 mL/hour (Ref). Optimal ACD-A regimens have not been identified; refer to institutional protocols as variations exist. Adjustment of ACD-A and calcium infusion rates is dependent on established protocols and ionized calcium concentrations.

CRRT calcium: Monitor ionized calcium concentrations in outflow (postfilter) limb of the CRRT circuit; maintain CRRT circuit ionized calcium between 1 to 1.4 mg/dL (0.25 to 0.35 mmol/L) (Ref).

Serum calcium: Monitor systemic ionized calcium peripherally (drawn directly from the patient), and maintain between 3.6 to 4.8 mg/dL (0.9 to 1.2 mmol/L) (Ref).

Adverse Reactions

Not applicable. This product is used in the extracorporeal blood processing with Autologous PRP systems in production of platelet rich plasma (PRP); it is not for direct intravenous infusion.

Contraindications

Direct intravenous infusion

Warnings/Precautions

Disease-related concerns:

• Hepatic impairment: When used for regional anticoagulation of the CRRT circuit: Use with caution in patients with liver impairment. Citrate is partially metabolized by the liver and may accumulate with hepatic impairment leading to toxicity. Considered contraindicated in patients with acute liver failure and blood transaminase values >1,000 units/L; however, if necessary, may be used with close monitoring and appropriate adjustments (Davenport 2021; Meersch 2018; Szamosfalvi 2021).

• Shock states: When used for regional anticoagulation of the CRRT circuit: Use with caution in patients with shock and hypoperfusion; may accumulate with hypoperfusion/shock states leading to toxicity. Considered contraindicated in patients with cardiogenic shock and blood lactate concentrations >8 mmol/L (Davenport 2021).

Other warnings/precautions:

• Appropriate use: Not intended for direct intravenous infusion into patients; when used in extracorporeal blood processing for the production of platelet rich plasma, must be used with the Autologous PRP system. Discard if closure system's biological barrier is not intact.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, In Vitro:

ACD Formula A: Citric acid 0.73 g, dextrose monohydrate 2.45 g, and sodium citrate dihydrate 2.2 g per 100 mL (500 mL [DSC], 1000 mL)

ACD-A noClot-50: Citric acid anhydrous 0.073 g, dextrose monohydrate 0.245 g, and sodium citrate dihydrate 0.22 g per 10 mL (50 mL)

Generic: Citric acid monohydrate 0.8 g, dextrose monohydrate 2.45 g, and sodium citrate dihydrate 2.2 g per 100 mL (750 mL [DSC])

Generic Equivalent Available: US

Yes

Pricing: US

Solution (ACD-A noClot-50 In Vitro)

0.73-2.45-2.2 g/100 mL (per mL): $0.75

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, In Vitro:

Generic: Citric acid 0.73 g, dextrose monohydrate 2.45 g, and sodium citrate dihydrate 2.2 g per 100 mL (500 mL, 1000 mL)

Use: Labeled Indications

Anticoagulant used in the extracorporeal blood processing with Autologous PRP systems in production of platelet rich plasma

Use: Off-Label: Adult

Regional anticoagulation for continuous renal replacement therapy circuit

Medication Safety Issues
Sound-alike/look-alike issues:

Anticoagulant citrate dextrose may be confused with anticoagulant sodium citrate

Metabolism/Transport Effects

None known.

Drug Interactions

There are no known significant interactions.

Monitoring Parameters

When used for regional anticoagulation of the CRRT circuit: Monitor serum electrolytes ~15 minutes and 1 hour after starting CRRT, then at least every 6 hours for CRRT; particularly monitor ionized calcium, sodium, potassium, chloride, magnesium, and bicarbonate to avoid metabolic abnormalities; acid-base balance; anion gap; for CRRT, monitor total body calcium at least once daily to calculate the calcium ratio (total calcium/ionized calcium) (calcium ratio may indicate citrate toxicity if >2.1); monitoring postfilter ionized calcium may be beneficial to ensure adequate anticoagulation of the dialysis circuit (Davenport 2021; KDIGO 2012).

Citrate accumulation may be managed by decreasing the blood flow rate (which decreases citrate requirements), increasing the dialysate rate (CVVHD) or the filtration rate (CVVH) to increase removal, or decreasing the targeted citrate concentration within the filter (Schneider 2017).

Mechanism of Action

Citrate ions induce anticoagulation by chelating free ionized calcium, making it unavailable for use in the coagulation system.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (CN) China: Anticoagulation
  1. ACD-A (anticoagulant citrate dextrose) [prescribing information]. Braintree, MA: Citra Labs; February 2015.
  2. Burry LD, Tung DD, Hallett D, et al. Regional citrate anticoagulation for PrismaFlex continuous renal replacement therapy. Ann Pharmacother. 2009;43(9):1419-1425. doi:10.1345/aph.1M182 [PubMed 19690224]
  3. Davenport A. Anticoagulation for continuous kidney replacement therapy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 27, 2021.
  4. Gupta M, Wadhwa NK, Bukovsky R. Regional citrate anticoagulation for continuous venovenous hemodiafiltration using calcium-containing dialysate. Am J Kidney Dis. 2004;43(1):67-73. doi:10.1053/j.ajkd.2003.09.014 [PubMed 14712429]
  5. Kidney Disease: Improving Global Outcomes (KDIGO). Summary of recommendation statements. Kidney Int Suppl (2011). 2012;2(1):8-12. doi:10.1038/kisup.2012.7 [PubMed 25018916]
  6. Kirwan CJ, Hutchison R, Ghabina S, et al. Implementation of a simplified regional citrate anticoagulation protocol for post-dilution continuous hemofiltration using a bicarbonate buffered, calcium containing replacement solution. Blood Purif. 2016;42(4):349-355. doi:10.1159/000452755 [PubMed 27866200]
  7. Meersch M, Zarbock A. Renal replacement therapy in critically ill patients: who, when, why, and how. Curr Opin Anaesthesiol. 2018;31(2):151-157. doi:10.1097/ACO.0000000000000564 [PubMed 29324487]
  8. Morabito S, Pistolesi V, Tritapepe L, Fiaccadori E. Regional citrate anticoagulation for RRTs in critically ill patients with AKI. Clin J Am Soc Nephrol. 2014;9(12):2173-2188. doi:10.2215/CJN.01280214 [PubMed 24993448]
  9. Ong SC, Wille KM, Speer R, Tolwani AJ. A continuous veno-venous hemofiltration protocol with anticoagulant citrate dextrose formula A and a calcium-containing replacement fluid. Int J Artif Organs. 2014;37(6):499-502. doi:10.5301/ijao.5000323 [PubMed 24811309]
  10. Schneider AG, Journois D, Rimmelé T. Complications of regional citrate anticoagulation: accumulation or overload? Crit Care. 2017;21(1):281. doi:10.1186/s13054-017-1880-1 [PubMed 29151020]
  11. Swartz R, Pasko D, O'Toole J, Starmann B. Improving the delivery of continuous renal replacement therapy using regional citrate anticoagulation. Clin Nephrol. 2004;61(2):134-143. doi:10.5414/cnp61134 [PubMed 14989634]
  12. Szamosfalvi B , Puri V, Sohaney R, et al. Regional citrate anticoagulation protocol for patients with presumed absent citrate metabolism. Kidney360. 2021;2(2)192-204. doi:10.34067/KID.0005342020. [PubMed 35373034]
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