Hydroxyethyl Starch 130/0.4

Brand name: Voluven
Drug class: Replacement Preparations
Chemical name: Starch 2-hydroxyethyl ether
CAS number: 9005-27-0

Introduction

Third-generation hydroxyethyl starch (HES) (tetrastarch); a nonprotein synthetic colloid used as a plasma volume expander.

Uses for Hydroxyethyl Starch 130/0.4

Hypovolemia

Prevention or treatment of hypovolemia.

Not a substitute for RBCs or coagulation factors in plasma.

Comparable with 6% hetastarch in 0.9% sodium chloride injection as a plasma volume expander in patients undergoing major elective orthopedic surgery.

Provides no mortality benefit over normal saline (0.9% sodium chloride injection) when used in patients admitted to the intensive care unit (ICU) and may be associated with an increased risk of severe renal injury (i.e., requirement for renal replacement therapy). Contraindicated in critically ill adults, including those with sepsis. (See Contraindications and also see Increased Mortality and Severe Renal Injury under Cautions.)

Hydroxyethyl Starch 130/0.4 Dosage and Administration

General

• In patients with severe dehydration, administer a crystalloid solution prior to administration of hydroxyethyl starch 130/0.4. Administer sufficient volume of fluid to avoid dehydration.

Administration

IV Administration

For solution and drug compatibility, see Compatibility under Stability.

Administer by IV infusion.

May administer repeatedly over several days; however, change administration sets at least once every 24 hours.

Discontinue infusion if an adverse reaction occurs.

Solution containing hydroxyethyl starch 130/0.4 in 0.9% sodium chloride injection is intended for single use only; discard unused portions.

Rate of Administration

Determine rate of infusion based on amount of blood lost, patient’s hemodynamic status, and resultant hemoconcentration (i.e., dilution effect of drug).

Infuse initial 10–20 mL slowly; closely observe patient for possible anaphylactoid reactions.

Dosage

Determine dosage based on amount of blood lost, patient's hemodynamic status, and resultant hemoconcentration (i.e., dilution effect of drug).

Pediatric Patients

Hypovolemia

IV

Determine dosage based on colloid needs of the patient, taking into account the patient's disease state and hemodynamic and hydration status.

Manufacturer recommends dosage of up to 3 g/kg (50 mL/kg) daily for all pediatric age groups.

In clinical studies, children <2 years of age received a mean dose of 0.96 g/kg (16 mL/kg), and children 2–12 years of age received a mean dose of 2.2 g/kg (36 mL/kg).

Adults

Hypovolemia

IV

Manufacturer recommends dosage of up to 3 g/kg (50 mL/kg) daily.

In clinical studies, a daily dosage of 30–270 g (500–4500 mL) has been used perioperatively in surgical patients, and a cumulative dose of 360–3960 g (6–66 L) has been used in ICU patients following traumatic brain injury.

Prescribing Limits

Pediatric Patients

Hypovolemia

IV

Children ≤18 years of age: Maximum 3 g/kg (50 mL/kg) daily.

Adults

Hypovolemia

IV

Maximum 3 g/kg (50 mL/kg) daily.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time. Contraindicated in patients with severe liver disease. (See Contraindications and also see Hepatic Impairment under Cautions.)

Renal Impairment

Avoid use in patients with preexisting renal impairment. (See Renal Impairment under Cautions and also see Pharmacokinetics.)

Geriatric Patients

Select dosage with caution. (See Geriatric Use and also see Renal Impairment under Cautions.)

Cardiac Insufficiency

Adjust dosage in patients with cardiac insufficiency. (See Hemodilution under Cautions.)

Cautions for Hydroxyethyl Starch 130/0.4

Contraindications

• Critically ill adult patients, including those with sepsis. (See Increased Mortality and Severe Renal Injury under Cautions.)

• Severe liver disease.

• Volume overload.

• Preexisting coagulation or bleeding disorders.

• Renal failure with oliguria or anuria not related to hypovolemia.

• Patients undergoing dialysis.

• Severe hypernatremia or severe hyperchloremia.

• Intracranial bleeding.

• Known hypersensitivity to HES.

Warnings/Precautions

Warnings

Increased Mortality and Severe Renal Injury

Increased mortality and/or severe renal injury requiring renal replacement therapy reported in critically ill adults, including patients with sepsis, receiving various HES preparations. Occurred within the recommended dosage range (30–90 g [500–1500 mL] daily). Considered by FDA to be class effects of HES.

HES solutions are contraindicated in critically ill adults, including those with sepsis. Avoid use in patients with preexisting renal dysfunction. Discontinue use at first sign of renal injury. Monitor renal function for >90 days in hospitalized patients receiving HES. (See Advice to Patients.)

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylactic and anaphylactoid reactions (e.g., mild influenza-like symptoms, bradycardia, tachycardia, bronchospasm, noncardiac pulmonary edema), reported very rarely.

If a hypersensitivity reaction occurs, discontinue therapy immediately; initiate appropriate treatment and supportive measures and continue until symptoms have resolved.

Other Warnings and Precautions

Hemodilution

Hemodilution, resulting in dilution of blood components (e.g., coagulation factors, other plasma proteins) and decreased hematocrit, reported. (See Hematologic Effects and Coagulopathy under Cautions.) Avoid fluid overload. (See Cardiac Insufficiency under Dosage and Administration.)

Hematologic Effects and Coagulopathy

Administration of high dosages may result in decreased concentrations of coagulation factors, other plasma proteins, and hematocrit. Depending on dosage administered, disturbances of blood coagulation beyond hemodilution effects also can occur rarely. Monitor coagulation parameters in patients receiving prolonged therapy or as clinically indicated.

Increased bleeding reported in patients undergoing open heart surgery with cardiopulmonary bypass who received HES. Excess bleeding occurred irrespective of molecular weight or molar substitution of the HES preparation, and, therefore, is considered by FDA to be a class effect of HES. Monitor coagulation status of patients undergoing open heart surgery in association with cardiopulmonary bypass. Discontinue HES at first sign of coagulopathy.

Pancreatic Effects

Transient elevations in serum amylase concentrations may occur; such elevations may obscure diagnosis of pancreatitis.

Cardiovascular Effects

Hypotension, shock, and circulatory collapse reported very rarely. Causal relationship to drug not established.

Patient Evaluation and Laboratory Monitoring

Monitor fluid balance, electrolyte concentrations, renal function, acid-base balance, and coagulation parameters in patients receiving prolonged therapy or as clinically indicated. Monitor liver function.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether hydroxyethyl starch 130/0.4 is distributed into human milk. Use with caution.

Pediatric Use

Safety and efficacy evaluated in limited number of infants <2 years of age undergoing elective surgery and in children 2–12 years of age undergoing cardiac surgery.

Use in adolescents >12 years of age is supported by evidence from well-controlled studies in adults.

Geriatric Use

No overall differences in safety or efficacy relative to younger adults, but increased sensitivity cannot be ruled out.

Principally eliminated by kidneys; because geriatric patients are more likely to have decreased renal function, select dosage with caution and monitor renal function for >90 days in hospitalized patients. (See Increased Mortality and Severe Renal Injury and also see Renal Impairment under Cautions.)

Hepatic Impairment

Monitor liver function. Contraindicated in patients with severe liver disease.

Renal Impairment

Possible increased risk of adverse reactions in patients with renal impairment; manufacturer and FDA recommend avoiding HES solutions, including hydroxyethyl starch 130/0.4, in patients with preexisting renal impairment. (See Contraindications and also see Increased Mortality and Severe Renal Injury under Cautions.)

Common Adverse Effects

Pruritus, increased serum amylase concentrations, hemodilution (resulting in decreased concentrations of coagulation factors, other plasma proteins, and hematocrit).

Interactions for Hydroxyethyl Starch 130/0.4

No known interactions with other drugs or nutritional preparations.

Hydroxyethyl Starch 130/0.4 Pharmacokinetics

Absorption

Bioavailability

No substantial plasma accumulation observed following daily administration of 500 mL of a 10% solution containing hydroxyethyl starch 130/0.4 (not commercially available in the US ) for 10 days.

Duration

Plasma volume expansion maintained for at least 6 hours following IV infusion of a 500-mL dose.

Special Populations

Renal impairment: In patients with Cl_cr <50 mL/minute, AUC increased by 73% compared with patients with Cl_cr >50 mL/minute; peak concentration unaffected by renal impairment.

Patients undergoing hemodialysis: No data available.

Pharmacokinetic data not available for patients with hepatic impairment, pediatric patients, or geriatric patients.

Distribution

Extent

Not known whether distributed into human milk.

Elimination

Metabolism

Hydroxyethyl starch 130/0.4 molecules larger than the renal threshold (molecular weight >70) are metabolized by plasma α-amylase.

Elimination Route

Primarily eliminated by the kidneys. Hydroxyethyl starch 130/0.4 molecules smaller than the renal threshold (molecular weight of <60) are excreted rapidly in urine. Molecules larger than the renal threshold are metabolized by plasma α-amylase before being excreted in urine.

Following administration of single or multiple 500-mL doses, approximately 62 or 70% of the dose, respectively, is excreted in urine as hydroxyethyl starch within 72 hours.

Half-life

12 hours.

Plasma concentrations remain at 75% of peak concentration 30 minutes following IV infusion, decrease to 14% at 6 hours postinfusion, and return to baseline levels at 24 hours postinfusion.

Special Populations

Renal impairment: In patients with Cl_cr <50 mL/minute, clearance decreased by 42% compared with patients with Cl_cr >50 mL/minute; terminal half-life unaffected by renal impairment.

Stability

Manufacturer states safety and compatibility with other additives not established.

Storage

Parenteral

Injection

15–25°C. Do not freeze.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Drug CompatibilityHID

Actions

• Third-generation HES (tetrastarch); synthetic colloid derived from thin boiling waxy corn starch composed mainly of amylopectin.

• Average molecular weight is approximately 130 (range: 110–150); molar substitution is 0.4 (approximately 40% of the glucose units of the starch are hydroxyethylated).

• Exhibits colloidal oncotic effects, resulting in plasma volume expansion. Plasma volume expansion comparable to that of hetastarch.

Advice to Patients

• Risk of severe kidney damage. Importance of immediately reporting signs and symptoms suggestive of kidney damage (e.g., change in frequency, volume, or color of urine; blood in urine; difficulty in urinating; swelling of the legs, ankles, feet, face, or hands; unusual weakness or fatigue; nausea and vomiting; shortness of breath).

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., CHF, liver disease, renal impairment).

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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