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Hetastarch (Hydroxyethyl starch; Hespan, Hextend): Drug information

Hetastarch (Hydroxyethyl starch; Hespan, Hextend): Drug information
(For additional information see "Hetastarch (Hydroxyethyl starch; Hespan, Hextend): Patient drug information" and see "Hetastarch (Hydroxyethyl starch; Hespan, Hextend): Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Mortality, kidney injury, and coagulopathy:

Use of hydroxyethyl starch (HES) products increases the risk of mortality, kidney injury, and coagulopathy.

Do not use HES products (ie, hetastarch) unless adequate alternative treatment is unavailable.

Brand Names: US
  • Hespan;
  • Hextend
Pharmacologic Category
  • Plasma Volume Expander, Colloid
Dosing: Adult
Granulocyte yield increase

Granulocyte yield increase (Hespan) (adjunctive agent): 250 to 700 mL; Note: Citrate anticoagulant is added before use and then the mixture is administered to the input line of the centrifuge apparatus.

Plasma volume expansion

Plasma volume expansion: Note: Discontinue use at the first sign of kidney injury. Do not use in the critically ill, those with sepsis or septic shock, those undergoing open heart surgery and cardiopulmonary bypass, or those with preexisting kidney impairment (SSC [Evans 2021]; manufacturer's labeling).

IV: 500 to 1,000 mL once; may repeat as needed based on assessment of intravascular volume status. Doses of more than 1,500 mL/day (~20 mL/kg) are usually not required.

Dosing: Kidney Impairment: Adult

Avoid use in patients with preexisting kidney impairment. Discontinue use at the first sign of kidney injury. Not eliminated by hemodialysis.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Hetastarch (Hydroxyethyl starch; Hespan, Hextend): Pediatric drug information")

Note: With severe dehydration, administer crystalloid first. Dose and rate of infusion are dependent on amount of blood lost, on maintenance or restoration of hemodynamics, and on amount of hemodilution. Titrate to individual colloid needs, hemodynamics, and hydration status. Do not use in critically ill patients, those undergoing open heart surgery with cardiopulmonary bypass, or those with preexisting kidney dysfunction. Critical Care Medicine societies (ACCM, SCCM) recommend against the use of hydroxyethyl starch (HES) solutions for fluid resuscitation of severe sepsis and septic shock in neonatal and pediatric patients (ACCM [Davis 2017]; SCCM [Dellinger 2013]).

Volume expansion

Volume expansion: Very limited data available: IV infusion: Children ≥1 year and Adolescents: 10 mL/kg/dose; dosing based on a small randomized, double-blinded study of 38 patients (age range: 1 to 15.5 years) compared hetastarch (n=20) and albumin (n=18) as a postoperative volume expander in the first 24 hours after congenital heart surgery; no differences in safety compared to albumin were found at hetastarch daily doses ≤20 mL/kg/day; patients receiving doses of 20 to 30 mL/kg/day were noted to have an increased PT; however, there was no difference in clinical bleeding; doses >30 mL/kg have not been studied (Brutocao 1996).

Dosing: Kidney Impairment: Pediatric

There are no pediatric-specific recommendation available; based on experience in adults, avoid use in patients with pre-existing renal dysfunction; use is contraindicated in renal failure with oliguria or anuria (not related to hypovolemia) and use should be discontinued at the first sign of renal injury.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling; based on experience in adult patients, use with caution.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined.

Cardiovascular: Increased plasma volume

Endocrine & metabolic: Hypervolemia, increased amylase (transient), metabolic acidosis

Hematologic & oncologic: Disorder of hemostatic components of blood (including Factor VIII deficiency, acquired von Willebrand's-like syndrome, dilutional coagulopathy), hemorrhage

Hepatic: Increased indirect serum bilirubin

Hypersensitivity: Hypersensitivity reaction (including anaphylaxis, angioedema, chest pain, erythema multiforme, fever, nonimmune anaphylaxis, severe hypotension, ventricular fibrillation)

Postmarketing:

Cardiovascular: Heart failure, lower extremity edema

Dermatologic: Pruritus

Gastrointestinal: Parotid gland enlargement, submaxillary gland enlargement, vomiting

Hematologic & oncologic: Anemia, disseminated intravascular coagulopathy (rare), hemolysis (rare), prolonged bleeding time

Nervous system: Headache, intracranial hemorrhage

Neuromuscular & skeletal: Myalgia

Renal: Acute kidney injury (Lagny 2016, Zarychanski 2013)

Respiratory: Flu-like symptoms, pulmonary edema

Contraindications

In patients when adequate alternative treatment is available.

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid reactions: Life-threatening anaphylactic/anaphylactoid reactions, including death, have been reported (rarely); discontinue use immediately with signs of hypersensitivity and administer appropriate therapy. Patients allergic to corn may be allergic to hetastarch.

• Bleeding/coagulopathy: Discontinue use of hydroxyethyl starch (HES) at the first sign of coagulopathy. Not recommended for use as a cardiac bypass pump prime, while the patient is on cardiopulmonary bypass, or in the period immediately afterward. HES solutions have been associated with excess bleeding in these patients. Monitor the coagulation status in patients undergoing open heart surgery in association with cardiopulmonary bypass. May cause coagulation abnormalities in conjunction with a reversible, acquired von Willebrand-like syndrome and/or factor VIII deficiency when used over a period of days. Consider replacement therapy if a severe factor VIII deficiency is detected. Coagulopathies may take several days to resolve. When used to prevent cerebral vasospasm in patients with subarachnoid hemorrhage (off-label use), significant clinical bleeding, intracranial bleeding, and death have been reported. Monitor the coagulation status of surgery patients due to excess bleeding with the administration of HES in this population.

• Fluid overload: Administration may cause fluid overload; use with caution in patients at risk from overexpansion of blood volume (eg, very young, older patients).

• Hematologic: Large volumes of hetastarch may cause a reduction in hemoglobin concentration, coagulation factors, and other plasma proteins due to hemodilution; when used for leukapheresis, frequent clinical evaluation and complete blood counts (CBC) are recommended. If leukapheresis frequency is greater than whole blood donation guidelines, consider monitoring total leukocyte and platelet counts, leukocyte differential, PT, and PTT as well. Coagulation may be impaired (eg, prolonged PT, PTT, and clotting times) and a transient prolongation of bleeding time may be observed.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Kidney impairment: Avoid use in patients with preexisting kidney impairment; monitor fluid status, urine output, and infusion rate; discontinue use at the first sign of kidney injury. Larger hetastarch molecules may leak into urine in patients with glomerular damage; may elevate urine specific gravity. Since the need for renal replacement therapy has been reported up to 90 days after HES administration, continue to monitor kidney function in all patients for at least 90 days.

• Thrombocytopenia: Use with caution in patients with thrombocytopenia; large volumes may interfere with platelet function and transiently prolong bleeding time. Observe for bleeding.

Special populations:

• Critically ill patients: Avoid use in critically ill adult patients, including those with sepsis and those admitted to the ICU. HES solutions have been associated with an increased risk of mortality in the critically ill (Brunkhorst 2008; Perel 2012; Perner 2012; SSC [Evans 2021]). Crystalloids (eg, sodium chloride and balanced solutions) are recommended as the fluid of choice for initial resuscitation and ongoing resuscitation (SSC [Evans 2021]. Avoid use in patients with preexisting kidney impairment and discontinue use at the first sign of kidney injury. Since the need for renal replacement therapy has been reported up to 90 days after HES administration, continue to monitor kidney function in all patients for at least 90 days.

Dosage form specific issues:

• Hextend: Contains calcium, lactate and potassium; use with caution in situations where electrolyte and/or acid-base disturbances may be exacerbated (kidney impairment, respiratory alkalosis, metabolic alkalosis). Do not use in leukapheresis.

Other warnings/precautions:

• Appropriate use: Not a substitute for red blood cells or coagulation factors.

Warnings: Additional Pediatric Considerations

Hetastarch use has been associated with acute kidney injury in pediatric patients (Reinhart 2012).

Dosage Forms: US

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

Solution, Intravenous:

Hespan: 6% (500 mL)

Hextend: 6% (500 mL)

Generic: 6% (500 mL)

Generic Equivalent Available: US

Yes

Pricing: US

Solution (Hespan Intravenous)

6-0.9% (per mL): $0.06

Solution (Hetastarch-NaCl Intravenous)

6-0.9% (per mL): $0.05

Solution (Hextend Intravenous)

6% (per mL): $0.23

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.

Administration: Adult

IV: Plasma volume expansion: Administer IV only; may be administered via infusion pump or pressure infusion. Administration rates vary depending upon the extent of blood loss, age, and clinical condition of patient but, in general, should not exceed 1.2 g/kg/hour (20 mL/kg/hour); however, rates up to 1,000 mL over 7 to 8 minutes via pressure infusion have been studied in otherwise healthy subjects (McIlroy 2003). Anaphylactoid reactions can occur, have epinephrine and resuscitative equipment available. If administered by pressure infusion, air should be withdrawn or expelled from bag prior to infusion to prevent air embolus. Do not administer Hextend with blood through the same administration set. Change IV tubing or flush copiously with normal saline before administering blood through the same line. Change IV tubing at least every 24 hours. Do not use if crystalline precipitate forms or is turbid deep brown.

Granulocyte yield increase: Mix Hespan and citrate well. Administer to the input line of the centrifuge apparatus at a ratio of 1:8 to 1:13 to venous whole blood.

Administration: Pediatric

Parenteral: Volume expansion: IV: Administer IV only; may be administered via infusion pump or pressure infusion; if administered by pressure infusion, air should be withdrawn or expelled from bag prior to infusion to prevent air embolus. Administration rates vary depending upon the extent of blood loss, age, and clinical condition of patient but, in general, should not exceed 1.2 g/kg/hour (20 mL/kg/hour) in adults. Change IV tubing or flush copiously with normal saline before administering blood through the same line. Do not administer Hextend with blood through the same administration set. Change IV tubing at least every 24 hours. Anaphylactoid reactions can occur; have epinephrine and resuscitative equipment available. Do not use if crystalline precipitate forms or is turbid deep brown.

Use: Labeled Indications

Granulocyte yield increase (Hespan only): Adjunct in leukapheresis to improve harvesting and increase the yield of granulocytes by centrifugation.

Plasma volume expansion: Treatment of hypovolemia to expand plasma volume in settings where adequate alternative treatment is unavailable.

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

Hespan may be confused with heparin

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Arbekacin: Hetastarch may enhance the nephrotoxic effect of Arbekacin. Risk X: Avoid combination

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies.

Breastfeeding Considerations

It is not known if hetastarch is present in breast milk. The manufacturer recommends that caution be exercised when administering hetastarch to breastfeeding women.

Monitoring Parameters

Plasma volume expansion: Assessment of intravascular volume status; BP, heart rate, urine output/kidney function (continue to monitor for at least 90 days after administration); serum electrolytes; acid-base balance; hemoglobin, hematocrit, coagulation parameters (especially in surgery patients), LFTs.

Granulocyte yield increase: CBC, total leukocyte and platelet counts, leukocyte differential count, hemoglobin, hematocrit, PT, PTT.

Mechanism of Action

Produces plasma volume expansion by virtue of its highly colloidal starch structure

Pharmacokinetics (Adult Data Unless Noted)

Duration: 3 to 36 hours

Excretion: Urine (~33% within 24 hours); smaller molecular weight molecules (<50,000 daltons) rapidly excreted.

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

  • (AE) United Arab Emirates: Haes steril | Hestar 200;
  • (AR) Argentina: Haes | Hessico | Lorihess | Voluven;
  • (AT) Austria: Elohaest isoton nacl | Expahes | Haes steril | Voluven;
  • (AU) Australia: Voluven;
  • (BD) Bangladesh: Voluven;
  • (BE) Belgium: Elohaes | Voluven;
  • (BG) Bulgaria: Haes steril;
  • (BR) Brazil: Expan | Haes steril | Istarhes | Plasmin | Venofundin | Voluven;
  • (CH) Switzerland: Haes steril | Voluven;
  • (CN) China: Haes-steril | Hetastarch 40 | Huo mu | Voluven;
  • (CO) Colombia: Hestar | Hidroxietil almidon | Nirhes | Nirhes 200 | Voluven;
  • (CZ) Czech Republic: Elohaest | Haes steril | Voluven;
  • (DE) Germany: Haes steril;
  • (EC) Ecuador: Voluven;
  • (EE) Estonia: Refortan | Stabisol | Voluven;
  • (EG) Egypt: Haes steril;
  • (ES) Spain: Elohes | Hes | Hesteril | Hidroxietil almidon | Voluven;
  • (FI) Finland: Voluven;
  • (FR) France: Heafusine | Hesteril | Pentastarch | Plasmohes | Voluven;
  • (GB) United Kingdom: Elohaes | Haes steril | Hespan | Hespan ahs | Pentaspan | Venofundin | Voluven;
  • (GR) Greece: Haes steril | Voluven;
  • (HK) Hong Kong: Voluven;
  • (HU) Hungary: Elohast | Expahes | Haes steril | Isohes | Osmohes | Plasmasteril | Voluven;
  • (ID) Indonesia: Farhes | Haes steril | Haes Steril Askes | Haes Steril Reg | Sanbe hest;
  • (IE) Ireland: Voluven;
  • (IN) India: Haes steril | Hestar | Ivstarch | Tetrahes;
  • (IT) Italy: Amidolite | Haes steril | Pentastarch | Voluven;
  • (JP) Japan: Hespander | Hestatt | Salinhes | Voluven;
  • (KE) Kenya: Haes steril | Hestar 200 | Voluven;
  • (KR) Korea, Republic of: Haes steril | Hemotasol | Hemotomin | Hesplasma | Hetastach | Hextend | Jeil pentastarch | Pentaspan | Pentastarch | Pentastarch in saline | Salinhes | Tetrahes | Voluven;
  • (KW) Kuwait: Haes steril | Voluven;
  • (LT) Lithuania: Refortan | Stabisol | Voluven;
  • (LU) Luxembourg: Haes steril;
  • (LV) Latvia: Refortan | Stabisol | Voluven;
  • (MX) Mexico: Hestar | Tetrastar | Voluven;
  • (MY) Malaysia: Haes steril | Voluven;
  • (NL) Netherlands: Elohaes | Haes steril;
  • (NO) Norway: Voluven;
  • (NZ) New Zealand: Pentaspan | Voluven;
  • (PH) Philippines: Haes steril | Sanbe hest | Tetrahes;
  • (PK) Pakistan: Haes steril;
  • (PL) Poland: Haes steril | Hes-hemodil | Hydroksyetyloskrobia | Plasmasteril | Voluven;
  • (PR) Puerto Rico: Hespan | Hextend | Pentaspan;
  • (PY) Paraguay: Hessico | Hidroxietil almidon demotek;
  • (RO) Romania: Refortan | Refortan plus;
  • (RU) Russian Federation: Haes steril | Hemohes | Hydrael 130 | Hydrael 200 | Hydroxyethyl starch 130 alium | Hydroxyethyl starch 200 | Hydroxyethyl starch 200 alium | Hydroxyethyl starch 200/0.5 | Hydroxyethylstarch | Ionokhes | Plasmaline | Plasmastabil 200 | Refortan | Refortan Hes | Refortan plus | Reohes 130 | Reohes 200 | Stabisol Hes | Volecam | Volecam haec | Volemcor | Voluven;
  • (SA) Saudi Arabia: Plasma steril | Voluven;
  • (SG) Singapore: Haes steril | Voluven;
  • (SI) Slovenia: Haes steril | Voluven;
  • (SK) Slovakia: Elohast | Haes steril | Voluven;
  • (TH) Thailand: Haes steril | Hespander | Hestar | Tetrahes | Voluven;
  • (TR) Turkey: Biohes | Bioplazma | Expahes | Haes steril | Isohes | Plasmasteril | Varihes | Voluhes;
  • (TW) Taiwan: 6-h.e.s. | Haes steril | Hesta | Hestar 200 pentastarch | Pentamo;
  • (UA) Ukraine: Geokodez | Haes steril | Hestar | Refordes | Refortan | Refortan N Hes | Refortan plus | Venofundin;
  • (UG) Uganda: Sanbe hest;
  • (UY) Uruguay: Haes steril;
  • (VE) Venezuela, Bolivarian Republic of: Hestar;
  • (ZA) South Africa: Voluven;
  • (ZM) Zambia: Hestar | Voluven;
  • (ZW) Zimbabwe: Hestar 200 | Voluven
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